A straightforward access to TMG-chitooligomycins and their evaluation as β-N-acetylhexosaminidase inhibitors

A chemo-biotechnological approach is reported for the synthesis of TMG-chitooligomycins, CO-n (NMe3). Their abilities to inhibit β-N-acetylhexosaminidases (HexNAcases), from Aspergillus oryzae (AoHex, fungi), Canavalia ensiformis (CeHex, plant) HexNAcases and a chitobiase from Serratia marcescens (SmCHB, bacteria) were studied and compared with their precursors CO-n (N). CO-n (NMe3) were revealed as potent inhibitors for AoHex and SmCHB with a proved chain length effect while CO-n (N) was a highly selective inhibitor of SmCHB. This route can be considered as the privileged way to produce easily and in large scale a wide range of size-defined chitooligosaccharide-based inhibitors to fine-tune the structure–activity relationships for inhibition of HexNAcases from various origins.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Chemo-biotechnological approach is described for access to TMG-chitooligomycins. ► CO-n (NMe3) and CO-n (N) were studied as HexNAcase inhibitors. ► The N-methyl quaternization as well as chitin chain length effect was studied.