Abstract
Sialidase transition-state analogue inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (Neu5Ac2en, DANA) has played a leading role in developing clinically used anti-influenza virus drugs. Taking advantage of the Neu5Ac2en-forming catalytic property of Streptococcus pneumoniae sialidase SpNanC, an effective one-pot multienzyme (OPME) strategy has been developed to directly access Neu5Ac2en and its C-5, C-9, and C-7-analogues from N-acetylmannosamine (ManNAc) and analogues. The obtained Neu5Ac2en analogues can be further derivatized at various positions to generate a larger inhibitor library. Inhibition studies demonstrated improved selectivity of several C-5- or C-9-modified Neu5Ac2en derivatives against several bacterial sialidases. The study provides an efficient enzymatic method to access sialidase inhibitors with improved selectivity.
Original language | English (US) |
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Pages (from-to) | 43-47 |
Number of pages | 5 |
Journal | ACS Catalysis |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Jan 5 2018 |
Keywords
- biocatalysis
- enzymatic synthesis
- Neu5Ac2en
- sialidase
- sialidase inhibitor
ASJC Scopus subject areas
- Catalysis