Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues

Chemical & Pharmaceutical Bulletin
Hiromi IiJun'ichi Uenishi

Abstract

γ-Glutamylcyclotransferase (GGCT) is an important enzyme that cleaves γ-glutamyl-amino acid in the γ-glutamyl cycle to release 5-oxoproline and amino acid. Eighteen N-acyl-L-alanine analogues including eleven new compounds have been synthesized and examined for their inhibitory activity against recombinant human GGCT protein. Simple N-glutaryl-L-alanine was found to be the most potent inhibitor for GGCT. Other N-glutaryl-L-alanine analogues having methyl and dimethyl substituents at the 2-position were moderately effective, while N-(3R-aminoglutary)-L-alanine, the substrate having an (R)-amino group at the 3-position or N-(N-methyl-3-azaglutaryl)-L-alanine, the substrate having an N-methyl substituent on the 3-azaglutaryl carbon, in constract, exhibited excellent inhibition properties.

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Citations

Feb 16, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Taku YoshiyaTatsuhiro Yoshiki

Related Concepts

Botch protein, human
Abufne
Dose-Response Relationship, Drug
Enzyme Inhibitors
Gamma-Glutamylcyclotransferase
Structure-Activity Relationship
Alanine
Analogs & derivatives
Carbon
Gamma-Glutamylcyclotransferase

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