Sialidase-catalyzed one-pot multienzyme (OPME) synthesis of sialidase transition-state analogue inhibitors.
ACS Catal
; 8(1): 43-47, 2018 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-29713561
ABSTRACT
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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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Catal
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos