Rational design of novel glycomimetics: inhibitors of concanavalin A

Karen T Welch; Trent A Turner; Callie E Preast

doi:10.1016/j.bmcl.2008.09.095

Rational design of novel glycomimetics: inhibitors of concanavalin A

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6573-5. doi: 10.1016/j.bmcl.2008.09.095. Epub 2008 Oct 1.

Authors

Karen T Welch¹, Trent A Turner, Callie E Preast

Affiliation

¹ Department of Chemistry, 250 Forest Dr., Georgia Southern University, Statesboro, GA 30460-8064, USA. kwelch@georgiasouthern.edu

PMID: 18990567
DOI: 10.1016/j.bmcl.2008.09.095

Abstract

A virtual screening approach was used to identify new glycomimetics. The National Cancer Institute Diversity Set was docked into the carbohydrate binding site of the lectin concanavalin A (ConA). The resulting poses were analyzed and 19 molecules were tested for inhibition with an enzyme-linked lectin assay (ELLA). Eight of the 19 molecules inhibited ConA-carbohydrate binding. The two most potent inhibitors have IC(50) values that are an order of magnitude smaller than the monosaccharide methyl alpha-D-mannopyranoside.

Publication types

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

MeSH terms

Amino Acid Motifs
Binding Sites
Carbohydrate Conformation
Catalytic Domain
Chemistry, Pharmaceutical / methods*
Concanavalin A / chemical synthesis*
Concanavalin A / chemistry
Concanavalin A / pharmacology*
Crystallography, X-Ray / methods
Drug Design
Fabaceae / metabolism
Inhibitory Concentration 50
Lectins / chemistry
Methylmannosides / chemistry
Models, Chemical
Molecular Conformation
Protein Binding

Substances

Lectins
Methylmannosides
Concanavalin A
methylmannoside