Synthesis and inhibitory activity of 8-substituted 2-deoxy-beta-KDO against CMP-KDO synthetase.
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.
Adachi
Hayamitsu
H
Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Kondo
Ken-Ichiro
K
Kojima
Fukiko
F
Umezawa
Yoji
Y
Ishino
Keiko
K
Hotta
Kunimoto
K
Nishimura
Yoshio
Y
D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D008956:Models, Chemical; D015394:Molecular Structure; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*
D004187:Disaccharides; D009713:Nucleotidyltransferases; C028984:3-deoxy-manno-octulosonate cytidyltransferase