Modified mannose disaccharides as substrates and inhibitors of a polyprenol monophosphomannose-dependent alpha-(1-->6)-mannosyltransferase involved in mycobacterial lipoarabinomannan biosynthesis.
A panel of alpha-(1-->6)-linked mannose disaccharides (5-8) in which the 2'-OH group has been replaced, independently, by deoxy, fluoro, amino, and methoxy functionalities has been synthesized. Evaluation of these compounds as potential substrates or inhibitors of a polyprenol monophosphomannose-dependent alpha-(1-->6)-mannosyltransferase involved in mycobacterial LAM biosynthesis demonstrated that the enzyme is somewhat tolerant substitution at this site. The enzyme recognizes the disaccharides with groups similar or smaller in size than the native hydroxyl (6-8), but not the disaccharide with the more sterically demanding methoxy group (5). The 2'-OH appears not form a critical hydrogen bonding interaction with the protein as the 2'-deoxy analog is a substrate for the enzyme.
Subramaniam
Vinodhkumar
V
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA.
Gurcha
Sudagar S
SS
Besra
Gurdyal S
GS
Lowary
Todd L
TL
D004187:Disaccharides / Q000378:metabolism; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D009682:Magnetic Resonance Spectroscopy; D008364:Mannosyltransferases / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D004187:Disaccharides; D008070:Lipopolysaccharides; C050016:lipoarabinomannan; D008364:Mannosyltransferases