8-取代的2-脱氧-β-KDO对CMP-KDO合成酶的合成及抑制活性

Synthesis and inhibitory activity of 8-substituted 2-deoxy-beta-KDO against CMP-KDO synthetase.

作者信息

Adachi Hayamitsu, Kondo Ken-Ichiro, Kojima Fukiko, Umezawa Yoji, Ishino Keiko, Hotta Kunimoto, Nishimura Yoshio

机构信息

Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

出版信息

Nat Prod Res. 2006 Apr;20(4):361-70. doi: 10.1080/14756360500183699.

DOI:10.1080/14756360500183699

PMID:16644531

Abstract

3-Deoxy-D-manno-octulosonate cytidyltransferase (CMP-KDO synthetase) is involved in the biosynthesis of lipopolysaccharide (LPS) which is an essential component of the outer membrane of gram-negative bacteria. New CMP-KDO synthetase inhibitors, 8-substituted derivatives of 2-deoxy-beta-KDO (2) have been prepared. Compounds 8, 11, 15 and 16 in which the 8-hydroxyl group of 2 is replaced by guanidine, di(carbamoylethyl)amino, p-methoxy- or p-nitro-benzyloxycarbonylamino, respectively affect moderately the CMP-KDO synthetase activity.

摘要

3-脱氧-D-甘露糖辛酮酸胞苷转移酶（CMP-KDO合成酶）参与脂多糖（LPS）的生物合成，脂多糖是革兰氏阴性菌外膜的重要组成部分。已制备出新型CMP-KDO合成酶抑制剂，即2-脱氧-β-KDO（2）的8-取代衍生物。化合物8、11、15和16中，2的8-羟基分别被胍基、二（氨甲酰乙基）氨基、对甲氧基或对硝基苄氧羰基氨基取代，它们对CMP-KDO合成酶活性有中度影响。