Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate: Potent inhibitors of glutamate carboxypeptidase II

Takashi Tsukamoto; Juliet M. Flanary; Camilo Rojas; Barbara S. Slusher; Nadya Valiaeva; James K. Coward

doi:10.1016/S0960-894X(02)00360-8

Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate: Potent inhibitors of glutamate carboxypeptidase II

Takashi Tsukamoto, Juliet M. Flanary, Camilo Rojas, Barbara S. Slusher, Nadya Valiaeva, James K. Coward

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

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Abstract

Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate were tested for the ability to inhibit glutamate carboxypeptidase II (GCP II). All of the compounds inhibit GCP II with IC₅₀ values in the low nanomolar range. The comparison of the results to previously reported inhibitory studies of the same compounds toward folylpoly-γ-glutamyl synthetase (FPGS) and γ-glutamyl hydrolase (γ-GH) provides insight into structural and mechanistic features of each enzyme. Potential utility of these compounds as diagnostic agents and probes to understand folate or antifolate poly-γ-glutamates metabolism is also described.

Original language	English (US)
Pages (from-to)	2189-2192
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	12
Issue number	16
DOIs	https://doi.org/10.1016/S0960-894X(02)00360-8
State	Published - Aug 19 2002
Externally published	Yes

ASJC Scopus subject areas

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

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10.1016/S0960-894X(02)00360-8

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title = "Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate: Potent inhibitors of glutamate carboxypeptidase II",

abstract = "Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate were tested for the ability to inhibit glutamate carboxypeptidase II (GCP II). All of the compounds inhibit GCP II with IC50 values in the low nanomolar range. The comparison of the results to previously reported inhibitory studies of the same compounds toward folylpoly-γ-glutamyl synthetase (FPGS) and γ-glutamyl hydrolase (γ-GH) provides insight into structural and mechanistic features of each enzyme. Potential utility of these compounds as diagnostic agents and probes to understand folate or antifolate poly-γ-glutamates metabolism is also described.",

author = "Takashi Tsukamoto and Flanary, {Juliet M.} and Camilo Rojas and Slusher, {Barbara S.} and Nadya Valiaeva and Coward, {James K.}",

note = "Funding Information: This research was supported, in part, by a grant from the National Cancer Institute to J.K.C., CA28097. ",

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doi = "10.1016/S0960-894X(02)00360-8",

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T1 - Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate

T2 - Potent inhibitors of glutamate carboxypeptidase II

AU - Tsukamoto, Takashi

AU - Flanary, Juliet M.

AU - Rojas, Camilo

AU - Slusher, Barbara S.

AU - Valiaeva, Nadya

AU - Coward, James K.

N1 - Funding Information: This research was supported, in part, by a grant from the National Cancer Institute to J.K.C., CA28097.

PY - 2002/8/19

Y1 - 2002/8/19

N2 - Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate were tested for the ability to inhibit glutamate carboxypeptidase II (GCP II). All of the compounds inhibit GCP II with IC50 values in the low nanomolar range. The comparison of the results to previously reported inhibitory studies of the same compounds toward folylpoly-γ-glutamyl synthetase (FPGS) and γ-glutamyl hydrolase (γ-GH) provides insight into structural and mechanistic features of each enzyme. Potential utility of these compounds as diagnostic agents and probes to understand folate or antifolate poly-γ-glutamates metabolism is also described.

AB - Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate were tested for the ability to inhibit glutamate carboxypeptidase II (GCP II). All of the compounds inhibit GCP II with IC50 values in the low nanomolar range. The comparison of the results to previously reported inhibitory studies of the same compounds toward folylpoly-γ-glutamyl synthetase (FPGS) and γ-glutamyl hydrolase (γ-GH) provides insight into structural and mechanistic features of each enzyme. Potential utility of these compounds as diagnostic agents and probes to understand folate or antifolate poly-γ-glutamates metabolism is also described.

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Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate: Potent inhibitors of glutamate carboxypeptidase II

Abstract

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