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†

Rani A. Jose,‡^a Arnout Voet,‡^bc Katleen Broos,‡^d Arjen J. Jakobi,^e Gilles Bruylants,^f Brecht Egle,^a Kam Y. J. Zhang,^c Marc De Maeyer,^b Hans Deckmyn^d and Wim M. De Borggraeve*^a

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^a Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Heverlee, Belgium
E-mail: wim.deborggraeve@chem.kuleuven.be
Fax: +32 16327990
Tel: +32 16327693

^b Laboratory for Biomolecular Modelling, Department of Chemistry, Division of Biochemistry, Molecular and Structural Biology, KU Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee, Belgium

^c Zhang Initiative Research Unit, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Japan

^d Laboratory for Thrombosis Research, KU Leuven Campus Kortrijk, E. Sabbelaan 53, 8500 Kortrijk, Belgium

^e Crystal & Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands

^f Ingénierie des Nanosystèmes Moléculaires CP165/64, Université Libre de Bruxelles 50, Av. F. D. Roosevelt, 1050 Brussels, Belgium

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.

Chemical Communications

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

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

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