An integrated fragment based screening approach for the discovery of small molecule modulators of the VWF-GPIbα interaction

Rani A Jose; Arnout Voet; Katleen Broos; Arjen J Jakobi; Gilles Bruylants; Brecht Egle; Kam Y J Zhang; Marc De Maeyer; Hans Deckmyn; Wim M De Borggraeve

doi:10.1039/c2cc35269a

An integrated fragment based screening approach for the discovery of small molecule modulators of the VWF-GPIbα interaction

Chem Commun (Camb). 2012 Nov 28;48(92):11349-51. doi: 10.1039/c2cc35269a.

Authors

Rani A Jose¹, Arnout Voet, Katleen Broos, Arjen J Jakobi, Gilles Bruylants, Brecht Egle, Kam Y J Zhang, Marc De Maeyer, Hans Deckmyn, Wim M De Borggraeve

Affiliation

¹ Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Heverlee, Belgium.

PMID: 23072895
DOI: 10.1039/c2cc35269a

Abstract

An integrated approach comprising STD NMR screening, pharmacophore based analogue selection and a bioassay is presented for the discovery of a stabilizer of the clinically relevant VWF-GPIbα protein-protein interaction.

MeSH terms

Binding Sites
Molecular Docking Simulation
Platelet Glycoprotein GPIb-IX Complex / chemistry
Platelet Glycoprotein GPIb-IX Complex / metabolism*
Protein Binding
Protein Interaction Mapping
Protein Structure, Tertiary
Small Molecule Libraries / chemistry*
von Willebrand Factor / chemistry
von Willebrand Factor / metabolism*

Substances

Platelet Glycoprotein GPIb-IX Complex
Small Molecule Libraries
von Willebrand Factor