High-throughput substrate specificity studies of sialidases by using chemoenzymatically synthesized sialoside libraries

Harshal A. Chokhawala, Hai Yu, Xi Chen

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

(Chemical Equation Presented) Sialidases, or neuraminidases, are enzymes that cleave terminal sialic acid (Sia) residues from complex sialic acid-containing structures. They have been found in many animals and microorganisms and are important in various physiological and pathological processes. In order to understand the biological significance of diverse sialidases, it is important to study in detail the structural determinants of their natural substrates. Here, we report the synthesis of sialoside libraries containing para-nitro-phenol-tagged sialosides with different naturally occurring sialic acid forms, different sialyl linkages, and different penultimate monosaccharides using a highly efficient one-pot three-enzyme chemoenzymatic approach. By using these compounds in a 96-well plate-based colorimetric high-throughput screening platform, the diversity of substrate preference is shown for seven bacterial sialidases. The sialoside libraries and the screening method are convenient tools for unravelling the substrate specificity and the biological function of sialidases.

Original languageEnglish (US)
Pages (from-to)194-201
Number of pages8
JournalChemBioChem
Volume8
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Carbohydrates
  • Chemoenzymatic synthesis
  • High-throughput screening
  • Sialic acids
  • Sialidases

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'High-throughput substrate specificity studies of sialidases by using chemoenzymatically synthesized sialoside libraries'. Together they form a unique fingerprint.

  • Cite this