3.4.17.11: glutamate carboxypeptidase
This is an abbreviated version!
For detailed information about glutamate carboxypeptidase, go to the full flat file.
Word Map on EC 3.4.17.11
-
3.4.17.11
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methotrexate
-
prodrugs
-
high-dose
-
antibody-directed
-
leucovorin
-
hdmtx
-
methotrexate-induced
-
gene-directed
-
naaladase
-
gdept
-
antibody-enzyme
-
medicine
-
anti-cea
-
anti-carcinoembryonic
-
prodrug-activating
-
gcpii
-
2-pmpa
-
n-acetyl-aspartyl-glutamate
-
dampa
-
drug development
-
diagnostics
-
pharmacology
- 3.4.17.11
- methotrexate
-
prodrugs
-
high-dose
-
antibody-directed
- leucovorin
-
hdmtx
-
methotrexate-induced
-
gene-directed
- naaladase
-
gdept
-
antibody-enzyme
- medicine
-
anti-cea
-
anti-carcinoembryonic
-
prodrug-activating
- gcpii
- 2-pmpa
-
n-acetyl-aspartyl-glutamate
-
dampa
- drug development
- diagnostics
- pharmacology
Reaction
release of C-terminal glutamate residues from a wide range of N-acylating moieties, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl and pteroyl groups =
Synonyms
carboxypeptidase G, carboxypeptidase G1, carboxypeptidase G2, CPDG2, CPG2, folate hydrolase G2, glucarpidase, glutamate carboxypeptidase, glutamyl carboxypeptidase, N-pteroyl-L-glutamate hydrolase, pteroylmonoglutamic acid hydrolase G2
ECTree
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Substrates Products
Substrates Products on EC 3.4.17.11 - glutamate carboxypeptidase
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REACTION DIAGRAM
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzyl-L-glutamic acid + H2O
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzoic acid + L-glutamate
-
a prodrug
-
-
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diylcarbamoylimino])dipentanedioic acid + 2 H2O
(11aS,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one) + ?
-
-
-
-
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diyloxycarbonylimino])dipentanedioic acid + 2 H2O
3-hydroxybenzyl 4-hydroxybenzyl (11S,11aS,11'S,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate) + 2 N-carboxy-L-glutamate
-
-
-
-
?
(4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
a trifluorinated prodrug
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
(4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
a trifluorinated prodrug
-
-
?
(4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
a trifluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
2,4-dihydroxypteroyl-L-glutamic acid + H2O
2,4-dihydroxypteroate + L-Glu
-
-
-
-
?
3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoic acid + H2O
?
-
cognate drug
-
-
?
3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
3,5-difluorobenzoyl-L-glutamate + H2O
3,5-difluorobenzoate + L-glutamate
-
chemical exchange saturation transfer magnetic resonance study, i.e. CEST-MR to monitor the release of glutamate. CEST-MR affords the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo
-
?
3,5-difluorobenzoyl-L-glutamic acid + H2O
3,5-difluorobenzoic acid + L-glutamate
-
-
-
-
?
3-fluoro-4-[bis(2-chloroethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
4-amino-N10-methylpteroylaspartic acid + H2O
4-amino-N10-methylpteroate + Asp
-
-
-
-
?
4-aminobenzoyl-L-glutamic acid + H2O
4-aminobenzoate + glutamate
-
-
-
-
?
4-aminobenzoyl-L-glutamic acid + H2O
4-aminobenzoate + L-glutamate
-
-
-
?
4-[(2-chloroethyl)(2-methylsulphonyloxyethyl)amino]benzoic acid + H2O
?
-
cognate drug
-
-
?
4-[(2-chloroethyl)-(2-methylsulphonyloxyethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
4-[bis(2-iodoethyl)-amino]-phenyloxycarbonyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
7-hydroxy-methotrexate + H2O
7-hydroxy-4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
di-tert-butyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenyloxycarbonyl-L-glutamic acid + H2O
?
-
-
-
-
?
diallyl 4-[N-[4'-bis(2''-chloroethyl)aminophenyl]-N-methylcarbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid + H2O
?
-
-
-
-
?
diallyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid + H2O
?
-
-
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenoxy]carbonyl)-L-glutamic acid + H2O
(11aS)-7,8-dimethoxy-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one + ?
-
-
-
-
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenyl]carbamoyl)-L-glutamic acid + H2O
? + L-glutamate
-
-
-
-
?
N-benzyloxycarbonyl-L-aspartic acid + H2O
benzyl carbonate + L-Asp
-
-
-
-
?
N-benzyloxycarbonyl-L-glutamic acid + H2O
benzyl carbonate + L-Glu
-
no activity with D-glutamic acid
-
-
?
N-benzyloxycarbonyl-L-glutamine + H2O
benzyl carbonate + L-Gln
-
-
-
-
?
[4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
[4-[bis(2-hydroxyethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
inactivation of the antitumor drug
-
-
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
the pharmacolically active 6S-stereoisomer is degraded faster than the inactive 6R-stereoisomer
-
-
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
-
-
-
?
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
-
-
-
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
-
-
?
4-aminopteroate + Glu
-
i.e. aminopterin
-
-
?
4-aminopteroylglutamic acid + H2O
4-aminopteroate + Glu
-
i.e. aminopterin
-
-
?
5-formylpteroate + Glu
-
i.e. leucovorin
-
-
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
i.e. leucovorin
-
-
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
i.e. leucovorin
-
-
?
diethylstilbestrol + L-glutamate
-
-
-
-
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
the water soluble substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
-
-
?
folic acid + H2O
pteroic acid + glutamic acid
-
i.e. pteroyl-L-glutamic acid
-
r
folic acid + H2O
pteroic acid + glutamic acid
-
equilibrium lies far towards hydrolysis
-
r
folic acid + H2O
pteroic acid + glutamic acid
-
no activity with pteroyl-D-glutamic acid
-
r
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
highly reduced clearance of the drug in enzyme-defective patients leads to severe neutropenia, mucositis, nephrotoxicity, neurotoxicity, and elevation of liver enzymes in plasma
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
i.e. amethopterin
-
-
?
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
related toxicity, overview, rapid inactivation of methotrexate by CPDG2, the product DAMPA is eliminated more raoidly than methotrexate
i.e. DAMPA
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
-
-
-
?
?
-
-
releases the carboxy-terminal glutamyl moiety of derivatives of pteroyl-mono-L-glutamic acid
-
-
?
additional information
?
-
-
substituents on N5 of the pteridine ring decrease the velocity of hydrolysis
-
-
?
additional information
?
-
-
synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy, overview
-
-
?
additional information
?
-
-
specifically cleaves terminal glutamic acid amines
-
-
?
additional information
?
-
-
rapid hydrolysis occurs in linkages of the form RCO-Glu and RCO-Gln, whereas those of the form RCO-D-Glu (D-Glu-D-Glu and Z-D-Glu) are not attacked
-
-
?
additional information
?
-
-
no hydrolysis of glutamate or glutamine lacking a free carboxyl alpha-carboxyl
-
-
?
additional information
?
-
-
effects of carboxypeptidase G2 administration to patients with methotrexate-induce renal failure, overview
-
-
?
additional information
?
-
-
enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
-
-
?
additional information
?
-
-
half-lives of prodrugs and drugs, overview
-
-
?
additional information
?
-
-
specifically cleaves terminal glutamic acid amines
-
-
?
additional information
?
-
-
CPG2 cleaves folic acid to pteroic acid and activates a range of bifunctional alkylating agent and antibiotic prodrugs
-
-
?
additional information
?
-
-
enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
-
-
?
additional information
?
-
-
half-lives of prodrugs and drugs, overview
-
-
?
additional information
?
-
-
hydrolyzes the COOH-terminal glutamate of oligopeptides and N-benzyloxycarbonyl glutamates
-
-
?
additional information
?
-
-
lesser activity against aspartate COOH-terminal peptide linkages
-
-
?