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Streptococcus pneumoniae Sialidase SpNanB-Catalyzed One-Pot Multienzyme (OPME) Synthesis of 2,7-Anhydro-Sialic Acids as Selective Sialidase Inhibitors

2018; American Chemical Society; Volume: 83; Issue: 18 Linguagem: Inglês

10.1021/acs.joc.8b01519

1520-6904

An Xiao, Teri J. Slack, Yanhong Li, Dashuang Shi, Hai Yu, Wanqing Li, Yang Liu, Xi Chen,

Carbohydrate Chemistry and Synthesis

Streptococcus pneumoniae sialidase SpNanB is an intramolecular trans-sialidase (IT-sialidase) and a virulence factor that is essential for streptococcal infection of the upper and lower respiratory tract. SpNanB catalyzes the formation of 2,7-anhydro- N-acetylneuraminic acid (2,7-anhydro-Neu5Ac), a potential prebiotic that can be used as the sole carbon source of a common human gut commensal anaerobic bacterium. We report here the development of an efficient one-pot multienzyme (OPME) system for synthesizing 2,7-anhydro-Neu5Ac and its derivatives. Based on a crystal structure analysis, an N-cyclohexyl derivative of 2,7-anhydro-neuraminic acid was designed, synthesized, and shown to be a selective inhibitor against SpNanB and another Streptococcus pneumoniae sialidase SpNanC. This study demonstrates a new strategy of synthesizing 2,7-anhydro-sialic acids in a gram scale and the potential application of their derivatives as selective sialidase inhibitors.