High-throughput identification of fucosyltransferase inhibitors using carbohydrate microarrays

Marian C Bryan; Lac V Lee; Chi-Huey Wong

doi:10.1016/j.bmcl.2004.04.001

High-throughput identification of fucosyltransferase inhibitors using carbohydrate microarrays

Bioorg Med Chem Lett. 2004 Jun 21;14(12):3185-8. doi: 10.1016/j.bmcl.2004.04.001.

Authors

Marian C Bryan¹, Lac V Lee, Chi-Huey Wong

Affiliation

¹ Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

PMID: 15149672
DOI: 10.1016/j.bmcl.2004.04.001

Abstract

A noncovalent carbohydrate microarray was used to screen for possible inhibitors to fucosyltransferases, which are critical to the synthesis of inflammation mediators like sialyl Lewis x (SLe(x)). Inhibition was followed by observation of the transferred fucose on the carbohydrate array with the lectin Tetragonolobus purpureas. Of these compounds, four inhibitors with nanomolar Ki(s) were discovered, with three of the top five inhibitors exhibiting a common architecture.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Sugars / chemistry
Carbohydrate Sequence
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Fucosyltransferases / antagonists & inhibitors*
Fucosyltransferases / metabolism
Kinetics
Lotus / genetics
Molecular Sequence Data
Oligosaccharides / chemistry*
Oligosaccharides / isolation & purification
Plant Lectins / chemistry
Plant Lectins / pharmacology

Substances

Amino Sugars
Enzyme Inhibitors
Oligosaccharides
Plant Lectins
N-acetyllactosamine
Fucosyltransferases