Discovery of inhibitors of Shiga toxin type 2 by on-plate generation and screening of a focused compound library.
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.
Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 (Canada) http://www.chem.ualberta.ca/∼glyco/who/index.htm.
Somnath
S
Dasgupta
Pavel I
PI
Kitov
Joanna M
JM
Sadowska
David R
DR
Bundle
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism
D004791:Enzyme Inhibitors; D008024:Ligands; D022641:Shiga Toxin 2; D054852:Small Molecule Libraries
Shiga toxins; drug discovery; glycoarrays; haemolytic uremic syndrome; inhibitors