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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10798-10804
Number of pages7
JournalJournal of Organic Chemistry
Volume83
Issue number18
DOIs
StatePublished - Sep 21 2018

Fingerprint

Sialic Acids
Neuraminidase
Derivatives
Neuraminic Acids
Prebiotics
Virulence Factors
Bacteria
Carbon
Crystal structure
2,7-anhydro-N-acetylneuraminic acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Streptococcus pneumoniae Sialidase SpNanB-Catalyzed One-Pot Multienzyme (OPME) Synthesis of 2,7-Anhydro-Sialic Acids as Selective Sialidase Inhibitors. / Xiao, An; Slack, Teri J.; Li, Yanhong; Shi, Dashuang; Yu, Hai; Li, Wanqing; Liu, Yang; Chen, Xi.

In: Journal of Organic Chemistry, Vol. 83, No. 18, 21.09.2018, p. 10798-10804.

Research output: Contribution to journalArticle

Xiao, An ; Slack, Teri J. ; Li, Yanhong ; Shi, Dashuang ; Yu, Hai ; Li, Wanqing ; Liu, Yang ; Chen, Xi. / Streptococcus pneumoniae Sialidase SpNanB-Catalyzed One-Pot Multienzyme (OPME) Synthesis of 2,7-Anhydro-Sialic Acids as Selective Sialidase Inhibitors. In: Journal of Organic Chemistry. 2018 ; Vol. 83, No. 18. pp. 10798-10804.
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abstract = "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.",
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