Synthesis and GGCT Inhibitory Activity of <i>N</i>-Glutaryl-L-alanine Analogues
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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 <i>N</i>-acyl-L-alanine analogues including eleven new compounds have been synthesized and examined for their inhibitory activity against recombinant human GGCT protein. Simple <i>N</i>-glutaryl-L-alanine was found to be the most potent inhibitor for GGCT. Other <i>N</i>-glutaryl-L-alanine analogues having methyl and dimethyl substituents at the 2-position were moderately effective, while <i>N</i>-(3<i>R</i>-aminoglutary)-L-alanine, the substrate having an (<i>R</i>)-amino group at the 3-position or <i>N</i>-(<i>N</i>-methyl-3-azaglutaryl)-L-alanine, the substrate having an <i>N</i>-methyl substituent on the 3-azaglutaryl carbon, in constract, exhibited excellent inhibition properties.
- Chemical and Pharmaceutical Bulletin
Chemical and Pharmaceutical Bulletin 64(7), 785-792, 2016
The Pharmaceutical Society of Japan