Synthesis and inhibitory activity of oligosaccharide thiazolines as a class of mechanism-based inhibitors for endo-β-N-acetylglucosaminidases

Bing Li, Kaoru Takegawa, Tadashi Suzuki, Kenji Yamamoto, Lai Xi Wang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A facile synthesis of oligosaccharide-thiazoline derivatives of N-glycans as a novel class of inhibitors for endo-β-N-acetylglucosaminidases was described. It was found that the external sugar residues on the N-glycan core could enhance the inhibitory potency. While the Manβ1,4GlcNAc- and Man3GlcNAc-thiazolines were only moderate inhibitors, the large Man9GlcNAc-thiazoline demonstrated potent inhibitory activity, with an IC50 of 0.22 and 0.42 μM against the Arthrobacter enzyme (Endo-A) and the human endo-β-N-acetylglycosaminidase (hENGase), respectively. It was also observed that the oligosaccharide thiazolines could differentially inhibit endo-β-N-acetylglucosaminidases from different sources. These oligosaccharide thiazolines represent the first class of endo-β-N-acetylglucosaminidase inhibitors.

Original languageEnglish
Pages (from-to)4670-4675
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number8
DOIs
Publication statusPublished - Apr 15 2008

Fingerprint

Acetylglucosaminidase
Oligosaccharides
Polysaccharides
Arthrobacter
Sugars
Inhibitory Concentration 50
Derivatives
endo-alpha-sialidase
Enzymes

All Science Journal Classification (ASJC) codes

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

Cite this

Synthesis and inhibitory activity of oligosaccharide thiazolines as a class of mechanism-based inhibitors for endo-β-N-acetylglucosaminidases. / Li, Bing; Takegawa, Kaoru; Suzuki, Tadashi; Yamamoto, Kenji; Wang, Lai Xi.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 8, 15.04.2008, p. 4670-4675.

Research output: Contribution to journalArticle

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