Discovery of inhibitors of Shiga toxin type 2 by on-plate generation and screening of a focused compound library

Somnath Dasgupta; Pavel I Kitov; Joanna M Sadowska; David R Bundle

doi:10.1002/anie.201309436

Discovery of inhibitors of Shiga toxin type 2 by on-plate generation and screening of a focused compound library

Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1510-5. doi: 10.1002/anie.201309436. Epub 2014 Jan 22.

Authors

Somnath Dasgupta¹, Pavel I Kitov, Joanna M Sadowska, David R Bundle

Affiliation

¹ Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 (Canada) http://www.chem.ualberta.ca/∼glyco/who/index.htm.

PMID: 24453091
DOI: 10.1002/anie.201309436

Abstract

A new microtiter-plate-based method for the rapid generation and evaluation of focused compound libraries was developed and applied to screening ligand analogues for the E. coli Shiga-like toxin Stx2a. The method is general, it mitigates the masking of intrinsic affinity gains by multivalency and enables the discovery of potential hits when starting from ligands that exhibit extremely low affinity with proteins that depend on multivalency for their function.

Keywords: Shiga toxins; drug discovery; glycoarrays; haemolytic uremic syndrome; inhibitors.

Publication types

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

MeSH terms

Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / metabolism
Enzyme-Linked Immunosorbent Assay
Escherichia coli / metabolism
Ligands
Protein Binding
Shiga Toxin 2 / antagonists & inhibitors*
Shiga Toxin 2 / metabolism
Small Molecule Libraries / chemistry*
Small Molecule Libraries / metabolism

Substances

Enzyme Inhibitors
Ligands
Shiga Toxin 2
Small Molecule Libraries