文章基本信息

标题：Dipeptides Containing L-Arginine Analogs : New Isozyme-Selective Inhibitors of Nitric Oxide Synthase
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作者：Nobutaka KOBAYASHI ; Tsunehiko HIGUCHI ; Yasuteru URANO 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1999
卷号：22
期号：9
页码：936-940
DOI：10.1248/bpb.22.936
出版社：The Pharmaceutical Society of Japan
摘要：Several L-arginine analogs are known as potent inhibitors of nitric oxide synthase (NOS). We recently synthesized dipeptides containing such amino acids, and found that they are potent and isozyme-selective NOS inhibitors. For example, S-methyl-L-isothiocitrullinyl-L-phenylalanine showed 66-fold selectivity for iNOS over nNOS, while S-methyl-L-isothiocitrullinyl-L-leucine and N^G-nitro-L-argininyl-L-phenylalanine showed 20- and 14-fold selectivity, respectively. Interestingly, S-methyl-L-isothiocitrullinyl-D-phenylalanine showed no selectivity, and S-methyl-L-isothiocitrullinyl-L-phenylalanine showed compective inhibition. These results suggest that each NOS isozyme has a cavity of different size near the C-terminal of the L-arginine binding site, and that the selectivity of inhibitors is due to the differences in the size of the cavity.
关键词：nitric oxide synthase;selective inhibitor;dipeptide;inducible nitric oxide synthase (iNOS);synthesis;Double-reciprocal plot