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.

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► 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.