Journal article
Inhibition of Glutamate Carboxypeptidase II by Phosphonamidothionate Derivatives of Glutamic Acid
Journal of enzyme inhibition and medicinal chemistry, Vol.16(4), pp.359-365
2001
Handle:
https://hdl.handle.net/2376/103934
PMID: 11916141
Abstract
A limited series of N-thiophosphonyl-glutamates were found to be inhibitors of the prostate-specific membrane antigen (PSMA) form of glutamate carboxypeptidase II. Comparative inhibitory profiles of an analogous O-thiophosphonyl-2-hydroxygluta-rate revealed that the amido-linkage of the N-thio-phosphonyl-glutamate provides a significant enhancement of inhibitory potency presumably due to significant hydrogen-bonding interactions with acceptor groups in the active-site of PSMA resulting in tighter binding. An analogous N-phosphonyl-glutamate exhibited significantly greater inhibitory potency than the parent N-thiophospho-nyl-glutamate indicating that the sulfur ligand of the N-thiophosphonyl-glutamates is responsible for less favorable active-site interactions than oxygen, potentially due to steric crowding from the longer P-S bond or as a result of active-site metal substitution of Co(II) for Zn(II) arising from assay conditions.
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Details
- Title
- Inhibition of Glutamate Carboxypeptidase II by Phosphonamidothionate Derivatives of Glutamic Acid
- Creators
- Chester E Rodriguez - 1Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA, 94132, USAHaiyan Lu - 1Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA, 94132, USAAlicia R Martinez - 1Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA, 94132, USAYing Hu - 1Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA, 94132, USAAlan Brunelle - 2Northwest Biotherapeutics Inc., 21720 23rd Drive SE, Bothell, WA, 98021, USAClifford E Berkman - 1Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA, 94132, USA
- Publication Details
- Journal of enzyme inhibition and medicinal chemistry, Vol.16(4), pp.359-365
- Academic Unit
- Chemistry, Department of
- Publisher
- Informa UK Ltd
- Identifiers
- 99900546804001842
- Language
- English
- Resource Type
- Journal article