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(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl) + H2O
?
a bradykinin-based peptide substrate QFS
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl) + H2O
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala + Phe-Lys-(2,4-dinitrophenyl)
bradykinin-based quenched fluorescent substrate assay
-
-
?
2 KFRRQRPRLSHKGPMPF + 2 H2O
KFRRQRPR + LSHKGPMPF + KFRRQRPRL + SHKGPMPF
-
-
-
ir
2 LVQPRGSRNGPGPWQGGRRKFRRQRPRLSHKGPMPF + 2 H2O
LVQPRGSRNGPGPWQGGRRKFRRQRPRL + SHKGPMPF + LVQPRGSRNGPGPWQGGRRKFRRQRPR + LSHKGPMPF
-
-
-
ir
2 pGlu-RPRLSHKGPMPF + 2 H2O
pGlu-RPRL + pGlu-RPR + SHKGPMPF + LSHKGPMPF
-
-
-
ir
2-aminobenzoyl-ARFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-AR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-DRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-DR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-FRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-FR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-HRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-HR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-IRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-IR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-KRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-KR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-LRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-LR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-NRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-NR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RAFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RA + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RDFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RD + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-REFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RE + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rGF-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Phe-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RGFK(Dnp)-OH + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl amide
-
-
-
-
ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rGL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Leu-N-(2,4dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Val-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RHFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RH + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RKFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RK + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RNFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RN + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RPFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RP + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RQFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RQ + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl amide
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rRL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Arg + Leu-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RSFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RS + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rSL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Ser + Leu-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RTFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RT + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-SRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-SR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-TRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-TR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-VRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-VR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-WRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-WR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-YRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-YR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
Abz-QRPRLSH-(3-nitro)Tyr + H2O
Abz-QRPRL + Ser-His-(3-nitro)Tyr
-
-
-
ir
adrenocorticotropic hormone + H2O
?
-
-
-
-
?
adrenomedullin + H2O
?
-
-
-
?
Ala-Leu-enkephalin + H2O
?
-
-
-
-
?
Aldolase + H2O
?
-
-
-
-
?
alpha-endorphin + H2O
?
-
-
-
?
alpha-neoendorphin + H2O
?
amyloid beta peptide + H2O
?
amyloid beta peptide Abeta42 + H2O
?
-
the peptide primarily undergoes degradation by NEP in vivo in the brain
-
-
?
amyloid beta peptide1-40 + H2O
?
amyloid beta peptide1-40 + H2O
amyloid beta peptide Asp1-Lys16 + amyloid beta peptide Asp1-Leu17 + amyloid beta peptide Asp1-Phe19
the wild-type enzyme cleaves Ab1-40 predominantly at Lys16-Leu17, Leu17-Val18 and Phe19-Phe20. The mutant G399V/G714K cleaves preferentially at Phe20-Ala21
main cleavage fragments after 60 min with the wild-type enzyme. After 360 min these fragments are degraded further, accompanied by the appearance of Val12-Leu17 and Tyr10-Leu17 fragments
-
?
amyloid beta peptide1-42 + H2O
?
amyloid beta(1-40) mutant A21G + H2O
?
-
Flemish variant of amyloid beta. Decreased degradation by neprilysin compared to either wild-type peptide or the other mutant peptides
-
-
?
amyloid beta(1-40) mutant D23N + H2O
?
-
Iowa variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22G + H2O
?
-
Arctic variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22K + H2O
?
-
Italian variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22Q + H2O
?
-
Dutch variant of amyloid beta
-
-
?
amyloid beta(1-40) peptide + H2O
?
-
-
-
-
?
amyloid-beta(1-7)AAC + H2O
?
a synthetic peptide, design and synthesis of a quenched fluorogenic peptide substrate qf-Abeta(1-7)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus
-
-
?
amyloid-beta(12-16)AAC + H2O
?
a synthetic peptide, design and synthesis of a quenched fluorogenic peptide substrate qf-Abeta(12-16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emits strong fluorescence upon cleavage. qf-Abeta(12-16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM can be detected at peptide concentration of 0.002 mM
-
-
?
amyloid-beta1-40 + H2O
Abeta1-16 + Abeta 1-17 + Abeta1-19
-
-
-
?
amyloid-beta4-40 + H2O
?
a synthetic peptide
-
-
?
amyloid-beta4-42 + H2O
?
a synthetic peptide
-
-
?
angiotensin + H2O
?
-
-
-
?
angiotensin III + H2O
?
-
-
-
-
?
angiotensin(1-9) + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
Arg-vasopressin + H2O
?
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
Atrial natriuretic factor + H2O
?
atrial natriuretic peptide + H2O
?
azocasein + H2O
?
-
-
-
-
?
Azocoll + H2O
?
-
-
-
-
?
benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
benzoyl-Gly-Gly-Arg + L-Leu-2-naphthylamide
-
-
-
-
?
benzyloxycarbonyl-Ala-Gly-Leu-Ala + H2O
?
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide + H2O
?
-
-
-
-
?
beta-amyloid peptide + H2O
?
-
-
-
-
?
beta-endorphin + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
beta-neoendorphin + H2O
?
brain natriuretic peptide + H2O
?
-
-
-
?
cholecystokinin-8 + H2O
?
D-Ala2-Leu5-enkephalin + H2O
?
-
-
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
D-Ala2-Leu5-enkephalinamide + H2O
?
-
-
-
-
?
dansyl-Gly-Trp-Gly + H2O
dansyl-Gly + Trp-Gly
-
-
-
?
dansyl-Gly-Tyr-Gly + H2O
dansyl-Gly + Tyr-Gly
-
-
-
?
dansyl-Gly-Tyr-Gly-NH2 + H2O
dansyl-Gly + Tyr-Gly-NH2
-
-
-
-
?
dynorphin A-10 + H2O
?
-
-
-
-
?
dynorphin A-13 + H2O
?
-
-
-
-
?
dynorphin A-17 + H2O
?
-
-
-
-
?
dynorphin A-6 + H2O
?
-
-
-
-
?
dynorphin A-8 + H2O
?
-
-
-
-
?
dynorphin A-9 + H2O
?
-
-
-
-
?
dynorphin(1-9) + H2O
?
-
-
-
-
?
exendin-4 + H2O
?
-
poor substrate
-
-
?
fibrinogen + H2O
fibrin + ?
galanin + H2O
?
-
-
-
-
?
gastri-releasing peptide + H2O
?
-
-
-
?
gastric inhibitor peptide + H2O
?
-
poor substrate
-
-
?
gastrin releasing peptide-10 + H2O
?
GLP-1(7-36)amide + H2O
?
-
insulinotropic peptide hormone
-
-
?
glucagon-like peptide 1 + H2O
?
-
-
-
-
?
glutaryl-Ala-Ala-Phe-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine + H2O
?
-
-
-
-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly + Phe-2-naphthylamide
-
-
-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly-Phe + 2-naphthylamine
-
-
-
-
?
Gly-Trp-Gly + H2O
?
-
-
-
-
?
haemoglobin + H2O
?
-
-
-
-
?
hippuryl-Arg-Arg-Ala-2-naphthylamide + H2O
hippuryl-Arg-Arg + Ala-2-naphthylamide
-
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
interleukin 1beta + H2O
?
Leu-2-naphthylamide + H2O
?
-
-
-
-
?
Leu-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin-Arg6 + H2O
?
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
leucine5-enkephalin + H2O
?
Tyr-Gly-Gly-Phe-Leu is cleaved at the Gly-Phe bond by the wild-type enzyme
-
-
?
Luliberin + H2O
?
-
poor substrate
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(Dnp)-OH + H2O
?
Mca-RPPGFSAFK-(Dnp) + H2O
?
-
-
-
?
Met-enkephalin + H2O
?
-
-
-
-
?
Met-enkephalin amide + H2O
?
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
Met5-enkephalin-Arg6 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide + H2O
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-L-phenylalanine + 4-methoxy-2-naphthylamine
-
-
-
?
N-acetyl-Gly-Trp-Gly + H2O
N-acetyl-Gly + Trp-Gly
-
-
-
-
?
N-benzyloxycarbonyl-Gly-Gly-Leu 2-naphthylamide + H2O
N-benzyloxycarbonyl-Gly-Gly + L-leucine 2-naphthylamide
-
-
-
?
N-benzyoxycarbonyl-Gly-Gly-Leu 2-naphthylamide + H2O
?
-
-
-
-
?
N-benzyoxycarbonyl-Gly-Gly-Leu-2-naphthylamide + H2O
N-benzyoxycarbonyl-Gly-Gly + L-Leu-2-naphthylamide
-
-
-
-
?
N-dansyl-Ala-Gly-D-(4-nitro-Phe)-Gly + H2O
?
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O
?
N-formyl-L-Met-Leu-Phe + H2O
?
-
the enzyme may play an important role in modulating chemotactic response by cleavage of the chemotactic substance N-formyl-Met-Leu-Phe
-
-
?
N-Formyl-Met-Leu-Phe + H2O
N-Formyl-Met + Leu-Phe
-
-
-
?
Na,K-ATPase alpha subunit + H2O
?
-
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Ala-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Phe-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Gly-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Neurokinin A + H2O
?
-
-
-
?
neuropeptide Y + H2O
truncated neuropeptide Y + C-terminal fragments of neuropeptide Y
-
-
neuropeptide Y 21-36 and 31-36 are the most abundant fragments generated in vivo
-
?
nociceptin + H2O
?
-
-
-
?
pBNP-26 + H2O
?
-
cleaved at several sites
-
-
?
pulmonary vasodilative vasoactive intestinal peptide + H2O
?
rapid inactivation
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
Secretin + H2O
?
-
-
-
-
?
somatostatin 14 + H2O
?
-
-
-
?
somatostatin 28 + H2O
?
-
-
-
?
striatal natriuretic factor + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
succinyl-Ala-Ala-Phe + 7-amino-4-methylcoumarin
succinyl-Ala-Ala-Phe-p-nitroanilide + H2O
?
-
-
-
-
?
succinyl-Arg-Arg-Leu-2-naphthylamide + H2O
succinyl-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
succinyl-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
sulfated cholecystokinin octapeptide + H2O
?
-
-
-
-
?
tachykinin + H2O
?
Q9I7I4
27.8% degradation
-
-
?
Tyr-D-Ala-Gly-Phe-Leu + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
Vasoactive intestinal peptide + H2O
?
-
-
-
-
?
Z-Ala-Ala-Leu-4-nitroanilide + H2O
Z-Ala-Ala-Leu + 4-nitroaniline
-
-
-
?
additional information
?
-
alpha-neoendorphin + H2O

?
-
-
-
-
?
alpha-neoendorphin + H2O
?
-
-
-
-
?
alpha-neoendorphin + H2O
?
-
-
-
-
?
alpha-neoendorphin + H2O
?
-
-
-
-
?
amyloid beta peptide + H2O

?
-
-
-
?
amyloid beta peptide + H2O
?
-
-
-
-
?
amyloid beta peptide + H2O
?
cleavage sites, overview
-
-
?
amyloid beta peptide + H2O
?
degradation
-
-
?
amyloid beta peptide1-40 + H2O

?
degradation
-
-
?
amyloid beta peptide1-40 + H2O
?
multiple cleavage sites
-
-
?
amyloid beta peptide1-40 + H2O
?
multiple cleavage sites, product peaks corresponding to Abeta1-16, Abeta1-17, Abeta10-17, Abeta20-28, Abeta20-29, and Abeta20-30. The C-terminal products result from the cleavages at K28-G29, G29-A30, and A30-I31. These products are derived from the trans-membrane region of the amyloid precursor protein (APP) from which Abeta is formed and are rather hydrophobic
-
-
?
amyloid beta peptide1-42 + H2O

?
-
-
-
?
amyloid beta peptide1-42 + H2O
?
-
-
-
-
?
amyloid beta peptide1-42 + H2O
?
degradation
-
-
?
amyloid beta peptide1-42 + H2O
?
multiple cleavage sites
-
-
?
amyloid-beta + H2O

?
-
-
-
?
amyloid-beta + H2O
?
degradation
-
-
ir
amyloid-beta1-40 + H2O

?
a synthetic peptide
-
-
?
amyloid-beta1-40 + H2O
?
degradation
-
-
ir
amyloid-beta1-42 + H2O

?
a synthetic peptide
-
-
?
amyloid-beta1-42 + H2O
?
degradation
-
-
ir
angiotensin I + H2O

?
Q9I7I4
51.6% degradation
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin II + H2O

?
-
-
-
-
?
angiotensin II + H2O
?
-
-
-
-
?
angiotensin II + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O

?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
i.e. substance P, seven peptides are produced
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O

?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
i.e. cholecystokinin-8, two distinct cleavage sites: Asp-Tyr(SO3H)-Met-Gly-/-Trp-Met-Asp-/-PheNH2, the splitting of the Asp7-Phe8NH2 bond proceeds 4-times more rapidly than the Gly4-Trp5 bond
-
-
?
Atrial natriuretic factor + H2O

?
-
human alpha atrial natriuretic peptide/cardiodilatin shows a single major cleavage site within the disulfide-linked loop between Cys and Phe in position 7 and 8
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
seven sites of hydrolysis: Arg4-Ser5, Cys7-Phe8, Arg11-Met12, Arg14-Ile15, Gly16-Ala17, Gly-20-Leu21, Ser25-Phe26. The initial attack takes place at a bond within the disulfide-linked loop and produces a peptide having the same amino acid composition as intact atrial natriuretic factor
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
dominant enzyme in the hydrolysis of atrial natriuretic factor
-
-
?
atrial natriuretic peptide + H2O

?
-
-
-
?
atrial natriuretic peptide + H2O
?
-
no activity with brain natriuretic peptide
-
-
?
atrial natriuretic peptide + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O

?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O

?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
bradykinin + H2O

?
Q9I7I4
27.8% degradation
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
cholecystokinin-8 + H2O

?
-
-
-
-
?
cholecystokinin-8 + H2O
?
-
-
-
-
?
D-Ala2-Leu5-enkephalin + H2O

Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
dynorphin + H2O

?
-
-
-
-
?
dynorphin + H2O
?
-
dynorphin A-6, A-8, A-9, A-10, A-13 and A-17
-
-
?
dynorphin + H2O
?
-
-
-
-
?
dynorphin + H2O
?
-
-
-
-
?
Elastin + H2O

?
-
-
-
?
endothelin-1 + H2O

?
-
-
-
?
endothelin-1 + H2O
?
-
-
-
-
?
endothelin-1 + H2O
?
-
-
-
?
enkephalin + H2O

?
-
-
-
?
enkephalin + H2O
?
-
hydrolysis at Gly3-Phe4
-
-
?
enkephalin + H2O
?
-
-
-
-
?
enkephalin + H2O
?
-
hydrolysis at Gly3-Phe4
-
-
?
enkephalin + H2O
?
-
hydrolysis at Gly3-Phe4
-
-
?
fibrinogen + H2O

fibrin + ?
inactivation, mechanism of NEP-mediated inactivation of fibrinogen through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin, overview
-
-
?
fibrinogen + H2O
fibrin + ?
fibrinogen from human and rat blood plasma, inactivation
-
-
?
FMRF amide + H2O

?
-
-
-
-
?
FMRF amide + H2O
?
-
-
-
-
?
FMRF amide + H2O
?
-
-
-
-
?
gamma-endorphin + H2O

?
-
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
-
?
gastrin + H2O

?
-
-
-
-
?
gastrin + H2O
?
-
-
-
-
?
gastrin + H2O
?
-
-
-
-
?
gastrin G-17 + H2O

?
-
-
-
-
?
gastrin G-17 + H2O
?
-
cleavage at four sites, Trp4-Leu5, Ala11-Tyr12, Gly13-Trp14 and Asp16-Phe17
-
-
?
gastrin G-17 + H2O
?
-
sulfated and unsulfated gastrin, cleavage is faster with the sulfated peptide
-
-
?
gastrin releasing peptide-10 + H2O

?
-
-
-
-
?
gastrin releasing peptide-10 + H2O
?
-
-
-
-
?
gastrin releasing peptide-10 + H2O
?
-
-
-
-
?
Glucagon + H2O

?
-
-
-
-
?
Glucagon + H2O
?
-
-
-
-
?
Glucagon + H2O
?
-
NEP24.11 is an important mediator of the degradation of both endogenous and exogenous glucagon in vivo
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O

glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O

hippuryl-Arg-Arg + Leu-2-naphthylamide
-
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O

His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
i.e. neurokinin A, hydrolysis at two sites: Ser5-Phe6 and Gly8-Leu9
-
-
?
insulin B chain + H2O

?
-
-
-
-
?
insulin B chain + H2O
?
multiple cleavage sites
-
-
?
insulin B chain + H2O
?
multiple cleavage sites, product analysis and cleavage sites preferences of wild-type and mutant neprilysins, cleavage sites, overview
-
-
?
insulin B chain + H2O
?
-
-
-
-
?
insulin B chain + H2O
?
-
-
-
-
?
interleukin 1beta + H2O

?
-
-
-
-
?
interleukin 1beta + H2O
?
-
-
-
-
?
interleukin 1beta + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O

?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalinamide + H2O

?
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O

?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(Dnp)-OH + H2O

?
-
-
-
?
Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(Dnp)-OH + H2O
?
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O

?
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
-
-
-
-
?
Met-Leu-Phe + H2O

?
-
chemotactic peptide
-
-
?
Met-Leu-Phe + H2O
?
-
chemotactic peptide
-
-
?
Met-Leu-Phe + H2O
?
-
chemotactic peptide
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O

?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O

?
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O
?
-
-
-
-
?
neurokinin B + H2O

?
-
-
-
-
?
neurokinin B + H2O
?
-
-
-
?
neurokinin B + H2O
?
-
-
-
-
?
neurokinin B + H2O
?
-
-
-
-
?
neurotensin + H2O

?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
cleaves at Pro10-Tyr11 and Tyr11-Ile12
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
oxytocin + H2O

?
-
-
-
-
?
oxytocin + H2O
?
-
-
-
-
?
oxytocin + H2O
?
-
-
-
-
?
physalaemin + H2O

?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O

pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
-
-
-
?
Substance P + H2O

?
Q9I7I4
85.8% degradation
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
cleaves at Gln6-Phe7, Phe7-Phe8, and Gly9-Leu10
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O

succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O

?
-
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O

succinyl-Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
succinyl-Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O

Tyr-D-Ala-Gly + Phe-Met
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
-
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O

Tyr-D-Ala-Gly + Phe-Met-NH2
-
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
-
-
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O

Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
additional information

?
-
-
NEP-1 plays an important role in the regulation of nematode locomation. NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in Caenorhabditis elegans
-
-
?
additional information
?
-
-
the enzyme may play an important role as regulator of plasma-derived peptides in the nephron
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
elevation of the enzyme activity in serum from underground coal miners exposed to chronic inhalation of coal mine dust particles. The enzyme reflects the chronic pulmonary inflammatory state induced by coalmine dust exposure, and so may be a marker of lung injury
-
-
?
additional information
?
-
-
the enzyme is involved in the processing of other peptide hormones
-
-
?
additional information
?
-
-
the enzyme is responsible for the difference in metabolism of sulfated and unsulfated gastrin in human circulation
-
-
?
additional information
?
-
-
the enzyme is the major inactivator of enkephalin in brain
-
-
?
additional information
?
-
-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
-
-
?
additional information
?
-
-
induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea. Caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. The combination of epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induces cellular neutral endopeptidase activity. The enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate
-
-
?
additional information
?
-
-
neutral endopeptidase 24.11/CD10 suppresses the progression of ovarian carcinomas
-
-
?
additional information
?
-
-
no activity with angiotensin (1-7)
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?
additional information
?
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hydrolysis of polypeptides between hydrophobic residues
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?
additional information
?
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a quenched fluorogenic peptide substrate containing the first seven residues of the Abeta peptide plus a C-terminal Cysteine residue is synthesized to detect neprilysin activity. A fluorophore is attached to the C-terminal Cysteine and its fluorescence is quenched by a quencher linked to the N-terminus of the peptide
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?
additional information
?
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the enzyme degrades a wide range of peptide substrates, physiologically relevant peptides are such as enkephalins, tachykinins, and natriuretic peptides
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?
additional information
?
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the enzyme directly interacts with phosphatidylserine and cardiolipin but not with cholesterol
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?
additional information
?
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the enzyme has broader substrate specificity and is a peptidase capable of cleaving a variety of physiological peptides
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?
additional information
?
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human neprilysin-2 has a more restricted substrate specificity compared to human neprilysin with less activity against several vasoactive peptides
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?
additional information
?
-
activity measurement optimization using the synthetic fluorogenic peptide substrates, evaluation and kinetics, overview
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-
additional information
?
-
activity measurement optimization using the synthetic fluorogenic peptide substrates, evaluation and kinetics, overview
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?
additional information
?
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analysis of intact amyloid-beta peptides and their NEP cleavage products by mass spectrometry. 73% of amyloid-beta4-40, 31% of amyloid-beta4-42, 45% of amyloid-beta1-40, and 18% of amyloid-beta1-42 degradation resulting from NEP catalyzed hydrolysis. Amyloid-beta4-9/amyloid-beta1-9, amyloid-beta10-17, and amyloid-beta20-30 are the major enzymatic products
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-
-
additional information
?
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analysis of intact amyloid-beta peptides and their NEP cleavage products by mass spectrometry. 73% of amyloid-beta4-40, 31% of amyloid-beta4-42, 45% of amyloid-beta1-40, and 18% of amyloid-beta1-42 degradation resulting from NEP catalyzed hydrolysis. Amyloid-beta4-9/amyloid-beta1-9, amyloid-beta10-17, and amyloid-beta20-30 are the major enzymatic products
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?
additional information
?
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in vitro NEP proteolysis generates fragments that lack the ability to bind to the apelin receptor, NEP fully inactivates apelin
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-
additional information
?
-
in vitro NEP proteolysis generates fragments that lack the ability to bind to the apelin receptor, NEP fully inactivates apelin
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?
additional information
?
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murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
-
murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
?
additional information
?
-
-
murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
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-
?
additional information
?
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-
catabolism of atrial and brain natriuretic peptide is independent of neutral endopeptidase. One or more other peptidase degrade atrial natriuretic peptide or brain natriuretic peptide in the heart, lungs and kidney
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-
?
additional information
?
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-
nicastrin controls neprilysin at a transcriptional level by contributing to the production of the beta-amyloid precursor protein intracellular domain with the gamma-secretase complex
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-
?
additional information
?
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
?
additional information
?
-
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
?
additional information
?
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-
the enzyme is the major inactivator of enkephalin in brain
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?
additional information
?
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-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
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?
additional information
?
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-
the enzyme is the major inactivator of enkephalin in brain
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?
additional information
?
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-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
-
-
?
additional information
?
-
-
in sepsis, the local concentration and action of adrenomedullin in tissue may be differentially regulated by NEP
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-
?
additional information
?
-
-
neutral endopeptidase inhibition has natriuretic and aquaretic actions in cirrhosis without any effect on blood pressure and kidney perfusion due to a significant overexpression of thgis enzyme in renal cortex
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-
?
additional information
?
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-
physiological role in metabolism of insect peptides at the synapse
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?
additional information
?
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-
-
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?
additional information
?
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-
could play an important role in the hydrolysis of neuropeptides
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?
additional information
?
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the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
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-
?
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(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Ala-Pro
-
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Leu-Tyr
-
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Ala
-
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Tyr
-
-
(2(R,S)-2-sulfanyl-2-isopropyl)acetyl-Ile-Tyr
-
-
(2R)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
(2R)-2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-ethyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3,4-oxadiazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[4-(2-methylpropyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]pentanoic acid
-
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid
-
-
(2R)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
-
(2S)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
(2S)-2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
(2S)-2-[(1-[[3-(4-chlorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
(2S)-2-[(1-[[3-(4-fluorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
(2S)-2-[[(2S)-1-[[(1S)-2-(biphenyl-4-yl)-1-carboxyethyl]amino]-5-methyl-1-oxohexan-2-yl]amino]-4-phenylbutanoic acid (non-preferred name)
-
-
(2S)-4-methoxy-2-([1-[(1-methyl-2-phenylethyl)carbamoyl]cyclopentyl]methyl)butanoic acid
-
-
(2S)-4-methoxy-2-[(1-[[(1R,2S)-2-(4-methoxyphenyl)cyclopropyl]carbamoyl]cyclopentyl)methyl]butanoic acid
-
-
(2S)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
-
(S)-N-[2-(phosphonomethylamino)-3-(4-biphenylyl)-propionyl]-3-aminopropionic acid
-
effects of neutral endopeptidase in acute inflammation in the lung are studied using a newly developed murine model of smoke and burn injury using NEP antagonist CGS-24592. Smoke and burn-induced lung injury and inflammation in mice pretreated with CGS-24592 is exacerbated, leading to more plasma extravasation and severe airway inflammation
2,3-Dimercaptopropan-1-ol
-
weak
2-(1-heptylcarbamoyl-cyclopentylmethyl)-4-methoxy-butyric acid tert-butyl ester
-
-
2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(2-sulfanylpropan-2-yl)phenyl]hexanoic acid
-
2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(3-sulfanylpentan-3-yl)phenyl]hexanoic acid
-
2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-1-(morpholin-4-yl)-5-sulfanylhexane-1,4-dione
-
2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-([1-[(1,3-benzodioxol-5-ylmethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1500 nM
2-([1-[(1-benzyl-2-hydroxyethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 384 nM
2-([1-[(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 313 nM
2-([1-[(1-ethyl-1H-1,2,3-triazol-4-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 82 nM
2-([1-[(3-ethylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1710 nM
2-([1-[(4-benzylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 96 nM
2-([1-[(4-butylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 184 nM
2-([1-[(4-carbamoylcyclohexyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 150 nM
2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 30 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-phenylbutanoic acid
-
IC50: 46 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-5-methylhexanoic acid
-
IC50: 120 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)hexanoic acid
-
IC50: 84 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 60 nM
2-([1-[(5-methyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 176 nM
2-([1-[(5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 283 nM
2-([1-[(6-methoxypyridazin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 374 nM
2-([1-[5-(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)-1,3,4-oxadiazol-2-yl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1139 nM
2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoic acid
-
2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid
-
2-methoxymethyl-3-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentyl]-propionic acid tert-butyl ester
-
-
2-[(1-[[(1R)-1-phenylethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 530 nM
2-[(1-[[(1R)-3-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 297 nM
2-[(1-[[(1R,2R)-2-benzylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 195 nM
2-[(1-[[(1R,2S)-2-propylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 890 nM
2-[(1-[[(3R)-1-benzylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 1060 nM
2-[(1-[[(3R)-1-carbamoylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 213 nM
2-[(1-[[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 700 nM
2-[(1-[[1-(hydroxymethyl)cyclopentyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 1710 nM
2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 96 nM
2-[(1-[[4-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 370 nM
2-[(1-[[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 124 nM
2-[(1-[[5-(cyclopropylmethyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 38 nM
2-[(3-iodo-4-hydroxy)phenylmethyl]-4-N-[3-hydroxyamino-3-oxo-1(phenylmethyl)propyl]amino-4-oxobutanoic acid
-
i.e. RB104, use of the inhibitor in detecting nanogram quantities of the enzyme by inhibitor gel electrophoresis
2-[(3-iodohydroxy)phenylmethyl]-4-N-[3-hydroxyamino-3-oxo-1-phenylmethylpropyl]-amino-4-oxobutanoic acid
-
i.e. RB104, highly selective and potent inhibitor
2-[1-(2-hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[1-(4-butyl-pyridin-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxybutyric acid benzyl ester
-
-
2-[1-(5-ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid
-
-
2-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[1-[3-(4-chloro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[1-[3-(4-fluoro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[[1-(1,3,4-thiadiazol-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 377 nM
2-[[1-(2,3-dihydro-1H-inden-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 313 nM
2-[[1-(5-benzyl-1,3,4-oxadiazol-2-yl)cyclopentyl]methyl]pentanoic acid
-
IC50: 3100 nM
2-[[1-(pyridin-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 1500 nM
3-[1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]propanoic acid
-
IC50: 237 nM
3-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentyl]-2-methoxymethyl-propionic acid tert-butyl ester
-
-
4-hydroxy-nonenal
-
intracellular neprilysin develops 4-hydroxy-nonenal adducts after 24 h of 4-hydroxy-nonenal treatment. 4-Hydroxy-nonenal-modified neprilysin shows decreased catalytic activity, which is associated with elevations in amyloid beta1-40 in SH-SY5Y and H4 APP695wt cells. Incubation of cells with amyloid beta1-42 also induces 4-hydroxy-nonenal adduction of neprilysin
4-methoxy-2-(1-phenethylcarbamoyl-cyclopentylmethyl)-butyric acid benzyl ester
-
-
4-methoxy-2-[1-(3-phenyl-propylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-(trans-2-pentyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[(trans-2-(4-fluorophenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[(trans-2-(4-methoxy-phenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[2-(4-methoxy-phenoxy)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[2-(4-methoxy-phenyl)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[3-(4-methoxy-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
6-(biphenyl-4-yl)-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[(1-acetylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[(1-benzoylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[(1-benzylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
-
AHU-377
-
LCZ696 comprises molecular moieties of valsartan, and of the NEP inhibitor prodrug AHU377 ((2R,4S)-5-biphenyl-4-yl-5-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester) (1:1 molar ratio). Oral administration of LCZ696 causes dose-dependent increases in atrial natriuretic peptide immunoreactivity due to NEP inhibition in Sprague-Dawley rats and provides sustained, dose-dependent blood pressure reductions in hypertensive double-transgenic rats
amyloid beta1-42
-
incubation of cells with amyloid beta1-42 induces 4-hydroxy-nonenal adduction of neprilysin. In an apparent compensatory response, amyloid beta-treated cells show increased neprilysin mRNA and protein expression. Despite elevations in neprilysin protein, the activity is significantly lower compared with the neprilysin protein level
-
atrial natriuretic factor
-
-
-
candoxatril
-
treatment increases plasma atrial natriuretic peptide levels and leads to significantly higher levels of atrial tissue cyclic GMP as well as plasma cyclic GMP. Candoxatril suppresses the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model
cis-4-[([1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentyl]carbonyl)amino]cyclohexanecarboxylic acid
-
-
diisopropyl fluorophosphate
-
-
DL-[N-(3-mercapto-2-benzylpropanoyl)]glycine
-
following neprilysin inhibition, islet amyloid deposition and beta-cell apoptosis increase by 54 and 75%, respectively
fasidotrilat
fasidotrilat interacts with the Arg664 of hNEP with more consistent bidentate hydrogen bonding and with the His658 with monodentate hydrogen bonding
Hg2+
0.001-0.05 mM, modifies the recombinant enzyme conformation, and highly reduces the enzyme activity. Hg2+ incubation increases NEP protein levels, but does not change NEP mRNA levels nor the levels of the amyloid intracellular domain peptide, a protein fragment with transcriptional activity. The Hg2+-induced inhibition of the enzyme activity may be mediated by a conformational change resulting in reduced amyloid beta1-42 degradation
Insulin B chain
inhibits the activity with substrate N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
LCZ696
-
LCZ696 is a dual-acting angiotensin II-receptor and neprilysin inhibitor (ARNI) in a single molecule: angiotensin-receptor blockade via its valsartan molecular moiety, and neprilysin inhibition via its AHU377 molecular moiety. In a randomized, double-blind, placebo-controlled, active comparator study it is shown that compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure
MCB3937
bifunctional inhibitor of NEP and DPP-IV
MCB4241
bifunctional inhibitor of NEP and DPP-IV
N-(2-benzyl-3-sulfanylpropanoyl)glycine
-
synthetic NEP inhibitor
N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-alanine
-
N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-tryptophan
-
N-([1-[(2S)-2-carboxy-3-[[N2-(methylsulfonyl)-L-lysyl]amino]propyl]cyclopentyl]carbonyl)-L-tyrosine
-
-
N-phenethylphosphonyl-L-leucyl-L-tryptophan
N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-Gly
-
-
N-[(2S)-3-phenyl-2-(sulfanylmethyl)propanoyl]-L-tryptophan
-
N-[1(R,S)-carboxy-2-phenylethyl]-Phe-p-aminobenzoate
-
-
N-[2-(4-bromobenzyl)-4-oxo-5-phenyl-5-sulfanylpentanoyl]-L-alanine
-
N-[2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoyl]-L-tryptophan
-
N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine
-
N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-tryptophan
-
N-[2-(4-bromobenzyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine
-
N-[2-(biphenyl-4-ylmethyl)-4-oxo-5-sulfanylhexanoyl]-L-alanine
-
N-[2-(biphenyl-4-ylmethyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine
-
N-[2-(biphenyl-4-ylmethyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine
-
N-[2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoyl]-L-leucine
-
N-[5-fluoresceinyl]-N'-[6-(3-mercapto-2-benzyl-1-oxopropyl)amino-1-hexyl]thiocarbamide
-
the inhibitor is a very potent probe for detecting membrane-bound enzyme for biological studies or diagnostic applications. Particularly useful for detecting the membrane-bound enzyme by flow cytometry
N-[N-[1(5)-carboxy-3-(4-hydroxyphenyl)propyl]-(5)-phenylalanyl]-(5)-isoserine
-
-
sacubitrilat
LBQ657, the inhibitor is bound to the active site of NEP by an intricate network of interactions that involves all functional groups of the compound giving rise to the high inhibitory potency. The catalytic zinc atom of NEP is ligated by the side chains of residues His583, His587, and Glu646 with the fourth coordination provided by the carboxylate oxygen adjacent to the P1 methyl of the compound, the backbone amide of LBQ657 forms H-bonding interactions with the side chains of Asn542 and Arg717. Enzyme active site binding structure, interaction, and inhibition mechanism, modelling, overview. All of the molecular interactions between LBQ657 and the enzyme are noncovalent, in line with a reversible inhibition mode
SCH48446
-
i.e. the diiodo analog of N-[N-[1(5)-carboxy-3-(4-hydroxyphenyl)propyl]-(5)-phenylalanyl]-(5)-isoserine
sialorphin
-
opiorphin homologue inhibits NEP
tert-butyl 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-methoxybutanoate
-
-
tris(2-carboxyethyl)phosphine
TCEP, strong inhibition
U46619
a thromboxane mimetic
1,10-phenanthroline

-
-
2-mercaptoethanol

-
-
amyloid beta

-
amyloid beta reduces global DNA methylation whilst increasing neprilysin DNA methylation and further suppressing the neprilysin expression in mRNA and protein levels. Amyloid beta induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in neprilysin expression along with a resultant increase in amyloid beta accumulation, and that amyloiud beta may induce global DNA hypo-methylation
-
amyloid beta
-
infusion with amyloid beta(25-35) induces decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-cAMP-response element binding protein CREB content and neprilysin levels
-
candoxatrilat

-
-
candoxatrilat
-
application restores vagal reflex bradycardia in old rats to levels similar to those in young neutral endopeptidase inhibitor-treated rats
dithiothreitol

-
-
EDTA

-
-
L-Cys

-
-
Leu5-enkephalin

-
-
Leu5-enkephalin
-
hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
Met5-enkephalin

-
-
Met5-enkephalin
-
hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
N-phenethylphosphonyl-L-leucyl-L-tryptophan

NPLT, synthesis of the phosphoramidon derivative with enhanced permeability into the skin that shows inability to inhibit type I and type IV collagenase, but inhibits fibroblast elastase
N-phenethylphosphonyl-L-leucyl-L-tryptophan
NPLT, synthesis of the phosphoramidon derivative with enhanced permeability into the skin that shows inability to inhibit type I and type IV collagenase, but inhibits fibroblast elastase
N-phenethylphosphonyl-L-leucyl-L-tryptophan
NPLT, synthesis of the phosphoramidon derivative with enhanced permeability into the skin that shows inability to inhibit type I and type IV collagenase, but inhibits fibroblast elastase
NaCl

-
brain enzyme; lung enzyme
NaCl
-
no inhibition of the enzyme from brain and kidney
phosphoramidon

-
-
phosphoramidon
a typical inhibitor for metalloproteinase
phosphoramidon
strong, consistent interactions with Arg664, Glu531 and His658 of hNEP
phosphoramidon
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
phosphoramidon
a typical inhibitor for metalloproteinase
phosphoramidon
-
neprilysin inhibition potentiates substance P-mediated neutrophil oxygen radical production and may promote other inflammatory activities during magnesium deficiency. Magnesium deficiency plus treatment with phosphoramidon reduces neprilysin activity by 48%, phosphoramidon or magnesium deficiency alone only reduce its activity by 26% and 15%, respectively
phosphoramidon
-
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
phosphoramidon
a typical inhibitor for metalloproteinase
phosphoramidon
-
synthetic NEP inhibitor
thiol

-
kidney enzyme; lung enzyme
thiol
-
intestine enzyme; kidney enzyme
thiorphan

-
-
thiorphan
complete inhibition
thiorphan
Arg49 and Arg664 act to support the ligand binding in NEP
thiorphan
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
thiorphan
-
thiorphan eliminates proteolysis of the alpha-subunit
thiorphan
1 mM, completely blocks neutral endopeptidase activity
thiorphan
-
plasma and lung A-type natriuretic peptide levels in rats treated with lipopolysaccharide are significantly higher than those in the control group, but are significantly decreased by thiorphan administration. Natriuretic peptide receptor-A mRNA levels do not differ significantly among the groups. Natriuretic peptide receptor-C mRNA levels in animals treated with lipopolysaccharide plus thiorphan group are significantly higher than those in the other groups
thiorphan
-
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
thiorphan
a NEP-specific inhibitor
thiorphan-NH2

-
-
valsartan

-
LCZ696 comprises molecular moieties of valsartan, and of the NEP inhibitor prodrug AHU377 ((2R,4S)-5-biphenyl-4-yl-5-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester) (1:1 molar ratio). Oral administration of healthy volunteers is associated with increases in plasma cGMP, renin concentration and activity, and angiotensin II, providing evidence for NEP inhibition and angiotensin receptor blockade
additional information

-
proteins derived from the Tat protein of HIV
-
additional information
-
both staurosporine-stimulated caspase-3 activation, p53 and neprilysin expression and activity are not affected by over-expression or depletion of presenilin complex component TMP21
-
additional information
no inhibition by 4-(2-butylbenzyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione and 4-(cyclopentylmethyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione
-
additional information
-
no inhibition by 4-(2-butylbenzyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione and 4-(cyclopentylmethyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione
-
additional information
desing of neprilysin inhibitors containing an alpha-mercaptoketone HSC(R1R2)CO group, as zinc ligand, substituted alpha-mercaptoketones are specific neprilysin inhibitors, optimization of the enzyme-inhibitor interactions within the S1 subsite, overview. Role of the size of the inhibitor which interacts with the S1, S1', or S2' domain of the enzyme and the nature of the substituents R1, and R2 of the mercaptoketone group in inhibitor potency. Introduction of a cyclohexyl chain in R1, R2 position and a (3-thiophen)benzyl group in position R3 yields to the most potent inhibitor of this series with a Ki value
-
additional information
structure-activity relationship studies. No or poor inhibition by 4-(2-aminoethyl)benzylsulfonyl fluoride (AEBSF), and Nalpha-tosyl-l-lysyl chloromethylketone (TLCK), and iodoacetamide
-
additional information
molecular docking studies, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues
-
additional information
-
molecular docking studies, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues
-
additional information
-
application of aldosterone, atrial natriuretic peptide, asymmetric dimethylarginine, and angiotensin peptides fail to cause down-regulation of renal neprilysin expression in vitro
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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0.0068 - 0.0224
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)
0.0687
2-aminobenzoyl-ARFK-2,4-dinitrophenyl ester
-
-
0.0178
2-aminobenzoyl-DRFK-2,4-dinitrophenyl ester
-
-
0.0097
2-aminobenzoyl-FRFK-2,4-dinitrophenyl ester
-
-
0.0161
2-aminobenzoyl-HRFK-2,4-dinitrophenyl ester
-
-
0.0093
2-aminobenzoyl-IRFK-2,4-dinitrophenyl ester
-
-
0.0528
2-aminobenzoyl-KRFK-2,4-dinitrophenyl ester
-
-
0.003
2-aminobenzoyl-LRFK-2,4-dinitrophenyl ester
-
-
0.0214
2-aminobenzoyl-NRFK-2,4-dinitrophenyl ester
-
-
0.0117
2-aminobenzoyl-RAFK-2,4-dinitrophenyl ester
-
-
0.0028
2-aminobenzoyl-RDFK-2,4-dinitrophenyl ester
-
-
0.0043
2-aminobenzoyl-REFK-2,4-dinitrophenyl ester
-
-
0.054
2-aminobenzoyl-rGF-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0259
2-aminobenzoyl-RGFK-2,4-dinitrophenyl amide
-
-
0.014
2-aminobenzoyl-RGFK-2,4-dinitrophenyl ester
-
-
0.0273
2-aminobenzoyl-rGL-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0089
2-aminobenzoyl-RHFK-2,4-dinitrophenyl ester
-
-
0.9981
2-aminobenzoyl-RKFK-2,4-dinitrophenyl ester
-
-
0.0024
2-aminobenzoyl-RNFK-2,4-dinitrophenyl ester
-
-
0.0075
2-aminobenzoyl-RPFK-2,4-dinitrophenyl ester
-
-
0.0121
2-aminobenzoyl-RQFK-2,4-dinitrophenyl ester
-
-
0.035
2-aminobenzoyl-RRFK-2,4-dinitrophenyl amide
-
-
0.0089
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester
-
-
0.028
2-aminobenzoyl-rRL-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0084
2-aminobenzoyl-RSFK-2,4-dinitrophenyl ester
-
-
0.0259
2-aminobenzoyl-rSL-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0108
2-aminobenzoyl-RTFK-2,4-dinitrophenyl ester
-
-
0.0081
2-aminobenzoyl-SRFK-2,4-dinitrophenyl ester
-
-
0.0095
2-aminobenzoyl-TRFK-2,4-dinitrophenyl ester
-
-
0.0109
2-aminobenzoyl-VRFK-2,4-dinitrophenyl ester
-
-
0.051
2-aminobenzoyl-WRFK-2,4-dinitrophenyl ester
-
-
0.0583
2-aminobenzoyl-YRFK-2,4-dinitrophenyl ester
-
-
0.0028
adrenocorticotropic hormone
-
-
-
0.109
Ala-Leu-enkephalin
-
wild type enzyme
0.024
alpha-endorphin
wild-type enzyme, pH and temperature not specified in the publication
0.135
alpha-neoendorphin
-
-
0.014 - 0.104
amyloid beta peptide1-40
-
0.0086
angiotensin
wild-type enzyme, pH and temperature not specified in the publication
0.0004 - 34.1
angiotensin I
0.179
angiotensin II
-
37°C, pH 7.4
0.1114
angiotensin(1-9)
-
37°C, pH 7.4
0.0062
Arg-vasopressin
wild-type enzyme, pH and temperature not specified in the publication
0.25
benzyloxycarbonyl-Ala-Gly-Leu-Ala
-
-
0.00654
beta-endorphin
-
-
0.296
cholecystokinin-8
-
-
0.07 - 2.137
D-Ala2-Leu5-enkephalin
0.773
D-Ala2-Leu5-enkephalinamide
-
-
0.432
D-Ala2-Met5-enkephalinamide
-
-
0.03
dansyl-Gly-Trp-Gly
-
-
0.041
dansyl-Gly-Tyr-Gly
-
-
0.09
dansyl-Gly-Tyr-Gly-NH2
-
-
0.0082
dynorphin A-17
-
-
0.053
endothelin-1
wild-type enzyme, pH and temperature not specified in the publication
0.013
gamma-endorphin
wild-type enzyme, pH and temperature not specified in the publication
0.15
gastri-releasing peptide
wild-type enzyme, pH and temperature not specified in the publication
0.049 - 0.068
gastrin G-17
0.024
GLP-1
wild-type enzyme, pH and temperature not specified in the publication
-
0.025
glucagon
wild-type enzyme, pH and temperature not specified in the publication
0.59
glutaryl-Ala-Ala-Phe-2-naphthylamide
-
-
0.12
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine
-
-
0.0685
glutaryl-Gly-Gly-Phe-2-naphthylamide
-
-
0.38
hippuryl-Arg-Arg-Ala-2-naphthylamide
-
-
0.35
hippuryl-Arg-Arg-Leu-2-naphthylamide
-
-
0.133
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2
-
-
0.074 - 0.2
Leu-enkephalin
0.612
Leu-enkephalinamide
-
-
0.086
Leu5-enkephalin
-
-
0.111
Leu5-enkephalin-Arg6
-
-
0.68
Leu5-enkephalinamide
-
-
0.755
Luteinizing hormone-releasing hormone
0.022 - 0.1
Met-enkephalin
0.41
Met-enkephalin amide
-
-
0.062
Met5-enkephalin
-
-
0.039
Met5-enkephalin-Arg6
-
-
0.05
Met5-enkephalin-Arg6Phe7
-
-
0.011 - 0.087
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
0.42
N-(4-carboxybutanoyl)-L-alanyl-L-alanyl-N-(4-methoxynaphthalen-2-yl)-L-phenylalaninamide
-
-
0.0408
N-2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.13
N-benzyoxycarbonyl-Gly-Gly-Leu 2-naphthylamide
-
-
0.3
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide
-
-
0.18
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide
-
-
0.11
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide
-
-
0.19
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide
-
-
0.11
Nalpha-benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide
-
-
0.08
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide
-
-
0.03
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide
-
-
0.0093
Neurokinin A
wild-type enzyme, pH and temperature not specified in the publication
0.022
neurokinin B
wild-type enzyme, pH and temperature not specified in the publication
0.016 - 0.078
neurotensin
0.02
nociceptin
wild-type enzyme, pH and temperature not specified in the publication
0.0074
somatostatin 14
wild-type enzyme, pH and temperature not specified in the publication
0.031
somatostatin 28
wild-type enzyme, pH and temperature not specified in the publication
0.043 - 0.073
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
0.058
succinyl-Ala-Ala-Phe-AMC
-
plasma enzyme
0.45
succinyl-Arg-Arg-Leu-2-naphthylamide
-
-
0.057
sulfated cholecystokinin octapeptide
-
-
0.018 - 0.019
Tyr-D-Ala-Gly-Phe-Leu
0.013
Tyr-D-Ala-Gly-Phe-Met
-
-
0.061 - 0.32
Tyr-D-Ala-Gly-Phe-met-NH2
0.008
Tyr-Gly-Gly-Phe-Met
-
-
0.033
unsulfated cholecystokinin octapeptide
-
-
0.0018
Vasoactive intestinal peptide
-
-
additional information
additional information
Michaelis-Menten profiles and steady-state kinetic parameters for cleavage of amyloid beta peptide1-40 and off-target peptide by wild-type and mutant enzymes, overview
-
0.0068
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)

pH 7.5, 37°C
0.0224
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)
pH 7.5, 37°C, in presence of activating K49-P1-20
0.014
amyloid beta peptide1-40

mutant G399V/G714K, pH and temperature not specified in the publication
-
0.042
amyloid beta peptide1-40
mutant G714K, pH and temperature not specified in the publication
-
0.055
amyloid beta peptide1-40
mutant G399V, pH and temperature not specified in the publication
-
0.104
amyloid beta peptide1-40
wild-type enzyme, pH and temperature not specified in the publication
-
0.0004
angiotensin I

-
-
34.1
angiotensin I
-
37°C, pH 7.4
0.005
bradykinin

-
-
0.032
bradykinin
wild-type enzyme, pH and temperature not specified in the publication
0.07
D-Ala2-Leu5-enkephalin

-
enzyme from tubules
0.076
D-Ala2-Leu5-enkephalin
-
enzyme from glomeruli
0.088
D-Ala2-Leu5-enkephalin
-
-
0.104
D-Ala2-Leu5-enkephalin
-
-
0.24
D-Ala2-Leu5-enkephalin
-
mutant enzyme R102M/N542G
1.399
D-Ala2-Leu5-enkephalin
-
mutant enzyme N542G
2.137
D-Ala2-Leu5-enkephalin
-
mutant enzyme R102M/N542G
0.049
gastrin G-17

-
sulfated
0.068
gastrin G-17
-
unsulfated
0.074
Leu-enkephalin

-
-
0.755
Luteinizing hormone-releasing hormone

-
-
0.755
Luteinizing hormone-releasing hormone
-
-
0.022
Met-enkephalin

-
-
0.011
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide

pH 6.5, 37°C, mutant NEPS546A
0.051
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, wild-type enzyme and mutant NEPF563V
0.073
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPS546T
0.074
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPS546E
0.081
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPF563L
0.083
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPF563I
0.087
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPF563M
0.016
neurotensin

wild-type enzyme, pH and temperature not specified in the publication
0.01
Substance P

-
-
0.016
Substance P
wild-type enzyme, pH and temperature not specified in the publication
0.043
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide

-
enzyme from amniotic fluid