Devadas B, Freeman S K, McWherter C A, Kishore N S, Lodge J K, Jackson-Machelski E, Gordon J I, Sikorski J A
Department of Medicinal and Structural Chemistry, G. D. Searle and Company, St. Louis, Missouri 63198, USA.
J Med Chem. 1998 Mar 12;41(6):996-1000. doi: 10.1021/jm980001q.
A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9 and 12 from (S)- or (R)-3-iodotyrosine and then grafting key enzyme recognition elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive Candida NMT inhibitors that bind to the peptide recognition site of the enzyme. Moreover, 16-18 have an affinity comparable to that of 2 even though they are devoid of peptide bonds. In contrast to 2, these nonpeptidic inhibitors exhibit antifungal activity.
从八肽ALYASKLS-NH2（2）出发，合成了一类新型的白色念珠菌NMT生物活性非肽抑制剂。合成策略包括从（S）-或（R）-3-碘酪氨酸制备新型保护的Ser-Lys模拟物9和12，然后逐步嫁接关键的酶识别元件。与2一样，化合物16、17和18是竞争性白色念珠菌NMT抑制剂，它们与该酶的肽识别位点结合。此外，尽管16 - 18没有肽键，但其亲和力与2相当。与2不同的是，这些非肽抑制剂具有抗真菌活性。
