Sialidase-Catalyzed One-Pot Multienzyme (OPME) Synthesis of Sialidase Transition-State Analogue Inhibitors

An Xiao, Yanhong Li, Xixuan Li, Abhishek Santra, Hai Yu, Wanqing Li, Xi Chen

Research output: Contribution to journalArticle

10 Scopus citations

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 languageEnglish (US)
Pages (from-to)43-47
Number of pages5
JournalACS Catalysis
Volume8
Issue number1
DOIs
StatePublished - Jan 5 2018

Keywords

  • biocatalysis
  • enzymatic synthesis
  • Neu5Ac2en
  • sialidase
  • sialidase inhibitor

ASJC Scopus subject areas

  • Catalysis

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