Synthesis of alkyl and cycloalkyl alpha-d-mannopyranosides and derivatives thereof and their evaluation in the mycobacterial mannosyltransferase assay.
The synthesis of a series of alkyl (having from C6 to C20 aglycones), cyclohexyl, and cyclohexylalkyl alpha-d-mannopyranosides, 6-deoxygenated analogs, thioglycosides, and sulfones derived thereof, is reported. Here, under the in vitro assay conditions used, none of the 15 tested compounds acted as an inhibitor of the mannose transfer catalyzed by the enzymes present in mycobacterial membrane and cell wall fractions. Mannopyranosides comprising shorter aliphatic, up to 8 carbon atoms long linear, or cyclic aglycone served as the acceptor substrates in the mycobacterial mannosyltransferase reaction. The thioglycosides exhibited similar behavior, in contrast to the sulfones, which were essentially not recognized by the mycobacterial enzymes. 6-Deoxygenated glycosides were not processed by the enzymes, suggesting that the mannose transfer occurs at position 6 of the acceptors.
Poláková
Monika
M
Institute of Chemistry, Center for Glycomics, GLYCOMED, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 38 Bratislava, Slovakia. Monika.Polakova@savba.sk
Belánová
Martina
M
Petrus
Ladislav
L
Mikusová
Katarína
K
D000478:Alkylation; D055162:Biocatalysis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008364:Mannosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000166:cytology / Q000201:enzymology*
D004791:Enzyme Inhibitors; D006027:Glycosides; D008364:Mannosyltransferases