Custom chemical microarray production and affinity fingerprinting for the S1 pocket of factor VIIa

• Published in: Analytical biochemistry 2004-12, Vol.335 (1), p.50-57
• Main Authors: Dickopf, Stefan, Frank, Michael, Junker, Hans-Dieter, Maier, Sabine, Metz, Günther, Ottleben, Holger, Rau, Harald, Schellhaas, Nathalie, Schmidt, Kristina, Sekul, Renate, Vanier, Cecile, Vetter, Dirk, Czech, Jörg, Lorenz, Martin, Matter, Hans, Schudok, Manfred, Schreuder, Herman, Will, David W., Nestler, Hans Peter
• Format: Article
• Language: English
• Subjects: Chemistry, Pharmaceutical; Combinatorial Chemistry Techniques; Drug Design; Factor VIIa - antagonists & inhibitors; Factor VIIa - chemistry; Factor VIIa - metabolism; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Weight; Organic Chemicals - chemical synthesis; Organic Chemicals - chemistry; Peptides - chemical synthesis; Peptides - chemistry; Protein Array Analysis; Protein Binding; Surface Plasmon Resonance
• ISSN: 0003-2697; 1096-0309
• DOI: 10.1016/j.ab.2004.08.033

The goal of this study was to explore the applicability of surface plasmon resonance (SPR)-based fragment screening to identify compounds that bind to factor VIIa (FVIIa). Based on pharmacophore models virtual screening approaches, we selected fragments anticipated to have a reasonable chance of binding to the S1-binding pocket of FVIIa and immobilized these compounds on microarrays. In affinity fingerprinting experiments, a number of compounds were identified to be specifically interacting with FVIIa and shown to fall into four structural classes. The results demonstrate that the chemical microarray technology platform using SPR detection generates unique chemobiological information that is useful for de novo discovery and lead development and allows the detection of weak interactions with ligands of low molecular weight.