Triazole-linked transition state analogs as selective inhibitors against V. cholerae sialidase

Teri J. Slack, Wanqing Li, Dashuang Shi, John B. McArthur, Gengxiang Zhao, Yanhong Li, An Xiao, Zahra Khedri, Hai Yu, Yang Liu, Xi Chen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Sialidases or neuraminidases are enzymes that catalyze the cleavage of terminal sialic acids from oligosaccharides and glycoconjugates. They play important roles in bacterial and viral infection and have been attractive targets for drug development. Structure-based drug design has led to potent inhibitors against neuraminidases of influenza A viruses that have been used successfully as approved therapeutics. However, selective and effective inhibitors against bacterial and human sialidases are still being actively pursued. Guided by crystal structural analysis, several derivatives of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en or DANA) were designed and synthesized as triazole-linked transition state analogs. Inhibition studies revealed that glycopeptide analog E-(TriazoleNeu5Ac2en)-AKE and compound (TriazoleNeu5Ac2en)-A were selective inhibitors against Vibrio cholerae sialidase, while glycopeptide analog (TriazoleNeu5Ac2en)-AdE selectively inhibited Vibrio cholerae and A. ureafaciens sialidases.

Original languageEnglish (US)
JournalBioorganic and Medicinal Chemistry
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Triazoles
Glycopeptides
Cholera
Neuraminidase
Vibrio cholerae
Sialic Acids
Glycoconjugates
Oligosaccharides
Viruses
Structural analysis
Pharmaceutical Preparations
Drug Design
Influenza A virus
Virus Diseases
Derivatives
Bacterial Infections
Crystals
Enzymes
2-deoxy-2,3-dehydro-N-acetylneuraminic acid
Therapeutics

Keywords

  • Carbohydrate
  • Glycopeptide
  • Neuraminidase
  • Sialidase
  • Sialidase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Triazole-linked transition state analogs as selective inhibitors against V. cholerae sialidase. / Slack, Teri J.; Li, Wanqing; Shi, Dashuang; McArthur, John B.; Zhao, Gengxiang; Li, Yanhong; Xiao, An; Khedri, Zahra; Yu, Hai; Liu, Yang; Chen, Xi.

In: Bioorganic and Medicinal Chemistry, 01.01.2018.

Research output: Contribution to journalArticle

Slack, Teri J. ; Li, Wanqing ; Shi, Dashuang ; McArthur, John B. ; Zhao, Gengxiang ; Li, Yanhong ; Xiao, An ; Khedri, Zahra ; Yu, Hai ; Liu, Yang ; Chen, Xi. / Triazole-linked transition state analogs as selective inhibitors against V. cholerae sialidase. In: Bioorganic and Medicinal Chemistry. 2018.
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