The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II

Brian Grella; Jessica Adams; James F. Berry; Greg Delahanty; Dana V. Ferraris; Pavel Majer; Chiyou Ni; Krupa Shukla; Scott A. Shuler; Barbara S. Slusher; Marigo Stathis; Takashi Tsukamoto

doi:10.1016/j.bmcl.2010.10.109

The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II

Brian Grella, Jessica Adams, James F. Berry, Greg Delahanty, Dana V. Ferraris, Pavel Majer, Chiyou Ni, Krupa Shukla, Scott A. Shuler, Barbara S. Slusher, Marigo Stathis, Takashi Tsukamoto

School of Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited potent inhibitory activity against GCPII. These indole-based compounds represent the first example of achiral GCPII inhibitors and demonstrate greater tolerance of the GCPII active site for ligands with significant structural difference from the endogenous substrate, N-acetyl-aspartylglutamate.

Original language	English (US)
Pages (from-to)	7222-7225
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2010.10.109
State	Published - Dec 15 2010

Keywords

Glutamate carboxypeptidase II
Indole
Inhibitor
Metallopeptidase
Thiol

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2010.10.109

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Grella, B., Adams, J., Berry, J. F., Delahanty, G., Ferraris, D. V., Majer, P., Ni, C., Shukla, K., Shuler, S. A., Slusher, B. S., Stathis, M., & Tsukamoto, T. (2010). The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II. Bioorganic and Medicinal Chemistry Letters, 20(24), 7222-7225. https://doi.org/10.1016/j.bmcl.2010.10.109

Grella, B, Adams, J, Berry, JF, Delahanty, G, Ferraris, DV, Majer, P, Ni, C, Shukla, K, Shuler, SA, Slusher, BS, Stathis, M & Tsukamoto, T 2010, 'The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 24, pp. 7222-7225. https://doi.org/10.1016/j.bmcl.2010.10.109

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abstract = "A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited potent inhibitory activity against GCPII. These indole-based compounds represent the first example of achiral GCPII inhibitors and demonstrate greater tolerance of the GCPII active site for ligands with significant structural difference from the endogenous substrate, N-acetyl-aspartylglutamate.",

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doi = "10.1016/j.bmcl.2010.10.109",

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AU - Adams, Jessica

AU - Berry, James F.

AU - Delahanty, Greg

AU - Ferraris, Dana V.

AU - Majer, Pavel

AU - Ni, Chiyou

AU - Shukla, Krupa

AU - Shuler, Scott A.

AU - Slusher, Barbara S.

AU - Stathis, Marigo

AU - Tsukamoto, Takashi

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AB - A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited potent inhibitory activity against GCPII. These indole-based compounds represent the first example of achiral GCPII inhibitors and demonstrate greater tolerance of the GCPII active site for ligands with significant structural difference from the endogenous substrate, N-acetyl-aspartylglutamate.

KW - Glutamate carboxypeptidase II

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KW - Inhibitor

KW - Metallopeptidase

KW - Thiol

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The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II

Abstract

Keywords

ASJC Scopus subject areas

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