Artigo Acesso aberto Revisado por pares

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

2017; American Chemical Society; Volume: 8; Issue: 1 Linguagem: Inglês

10.1021/acscatal.7b03257

ISSN

2155-5435

Autores

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

Tópico(s)

Carbohydrate Chemistry and Synthesis

Resumo

Sialidase transition state analog 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-analogs from N-acetylmannosamine (ManNAc) and analogs. The obtained Neu5Ac2en analogs 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.

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