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
orally available glutamate carboxypeptidase inhibitor E2072 (commercial preparation) has a neuroprotective effect on three well-established animal models of chemotherapy. It improves the chemotherapy-induced nerve conduction velocity deficits
Combined impact of polymorphism of folate metabolism genes; glutamate carboxypeptidase, methylene tetrahydrofolate reductase and methionine synthase reductase on breast cancer susceptibility in kashmiri women.
The potential of carboxypeptidase G2-antibody conjugates as anti-tumour agents. I. Preparation of antihuman chorionic gonadotrophin-carboxypeptidase G2 and cytotoxicity of the conjugate against JAR choriocarcinoma cells in vitro.
substitution leads to a high decrease in expression level (compared to wild type). Melting temperature is 53.4Â°C, compared to 60.4Â°C for wild-type enzyme. Mutation abolishes activity against methotrexate
substitution leads to a high decrease in expression level (compared to wild type). Melting temperature is 54.4C, compared to 60.4Â°C for wild-type enzyme. Mutation abolishes activity against methotrexate
overexpression of a codon-optimized gene in Escherichia coli, vector pET28a, the enzyme is expressed to about 60% of the total host protein and the purification of the recombinant His-tagged protein could be achieved in a single step by Ni2+ charged column chromatography
the enzyme is used in antibody directed enzyme prodrug therapy to catalyse the formation of an active drug from an inert prodrug. Free carboxypeptidase G2 in the bloodstream must be inhibited before administration of the prodrug in order to avoid a systemic reaction in the patient
side effects of methotrexate especially hepatotoxicity limits clinical applications of this anticancer agent. Carboxypeptidase G2 fused to the transactivator transduction domain (TAT) is administrated for the treatment of elevated plasma concentrations of methotrexate. TAT-CPG2 significantly prevents methotrexate-induced oxidative stress by decreasing the formation of reactive oxygen species (ROS) and increasing the content of glutathione (GSH) and catalase activity. Both native and denatured TAT-carboxypeptidase G2 strongly protect HepG2 cells against methotrexate-induced oxidative stress and apoptosis. Intracellular delivery of carboxypeptidase G2 might provide a new therapeutic strategy for protecting against methotrexate mediated cytotoxicity
design of a series of circular permutations of the medically important enzyme, carboxypeptidase G2, that show similar structure and stability to the wild-type, while retaining equivalent enzymatic activity in most cases. One of the circular permutants confers methotrexate resistance when expressed in Escherichia coli similarly to wild-type carboxypeptidase G2. The circular permutants provide a promising starting point for generating a protease regulatable form of carboxypeptidase G2, which will be valuable in advancing directed enzyme-prodrug chemotherapy technology
glutamate chemical exchange saturation transfer magnetic resonance imaging GluCEST-MRI is an attractive method for metabolic imaging of glutamate. The change in glutamate concentration measured with GluCEST MRI could provide a noninvasive biomarker of carboxypeptidase G2 activity, in addition to acting as a surrogate for prodrug activation and the concentration of activated drug in the tumor
glutamate carboxypeptidase inhibition is evident for a neuroprotective role in several chronic models of chemotherapy-induced peripheral neuropathy and claims an approach for the clinical treatment of this pathology
carboxypeptidase G2 is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene-directed enzyme prodrug therapy (GDEPT). These therapeutic strategies would benefit from robust imaging strategies that afford high spatial and temporal resolution images of the biodistribution of carboxypeptidase G2 activity. Employing dynamic nuclear polarization (DNP) and natural abundance 13C magnetic resonance spectroscopy (MRS), the carboxypeptidase G2-mediated conversion of a novel hyperpolarized reporter probe 3,5-difluorobenzoyl-L-glutamic acid to 3,5-difluorobenzoic acid and L-glutamic acid is observed in vitro. The potential for translation in vivo will primarily depend on the 13C relaxation times and this appears to be an important limiting factor in the case of 3,5-difluorobenzoyl-L-glutamic acid
A phase I study of single administration of antibody-directed enzyme prodrug therapy with the recombinant anti-carcinoembryonic antigen antibody-enzyme fusion protein MFECP1 and a bis-iodo phenol mustard prodrug