Synthesis of 1,2,3-Triazolo-Linked Octyl (1→6)-α-d-Oligomannosides and Their Evaluation in Mycobacterial Mannosyltransferase Assay

Abstract

The synthesis of conjugates consisting of two or three mannose units interconnected by a 1,2,3-triazole linker installed by the "click" reaction is reported. These conjugates were evaluated in mycobacterial mannosyltransferase (ManT) assay. Detailed analysis of the reaction products showed that these compounds with triazole linker between sugar moieties were tolerated by the enzyme, which elongated them by one or two sugar units with α-(1→6) linkage. The effectiveness of this transfer was reduced in comparison to that observed for the acceptor analogues containing a glycosidic linkage, but still, this is the first report on such unnatural compounds serving as substrates for mycobacterial ManT. The ability of the studied compounds to function as acceptors for the ManT suggests that the relative distance and spatial orientation of acceptor octyl hydrophobic aglycone (optimal length for the ManT) and free primary C-6 hydroxy group of the nonreducing terminal mannose unit (to which glycosyl residue is transferred by the mycobacterial ManT) are important for ManT activity, but at the same time, their variations are tolerated by the enzyme in a relatively wide range.