title: Custom chemical microarray production and affinity fingerprinting for the S1 pocket of factor VIIa.
abstract: 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.
authors.affiliation: Graffinity Pharmaceuticals AG, Im Neuenheimer Feld 518-519, D-69120 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dickopf
authors.forename: Michael
authors.initials: M
authors.lastname: Frank
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Junker
authors.forename: Sabine
authors.initials: S
authors.lastname: Maier
authors.forename: Günther
authors.initials: G
authors.lastname: Metz
authors.forename: Holger
authors.initials: H
authors.lastname: Ottleben
authors.forename: Harald
authors.initials: H
authors.lastname: Rau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schellhaas
authors.forename: Kristina
authors.initials: K
authors.lastname: Schmidt
authors.forename: Renate
authors.initials: R
authors.lastname: Sekul
authors.forename: Cecile
authors.initials: C
authors.lastname: Vanier
authors.forename: Dirk
authors.initials: D
authors.lastname: Vetter
authors.forename: Jörg
authors.initials: J
authors.lastname: Czech
authors.forename: Martin
authors.initials: M
authors.lastname: Lorenz
authors.forename: Hans
authors.initials: H
authors.lastname: Matter
authors.forename: Manfred
authors.initials: M
authors.lastname: Schudok
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
authors.forename: David W
authors.initials: DW
authors.lastname: Will
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Nestler
mesh_terms: D002626:Chemistry, Pharmaceutical; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008970:Molecular Weight; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D040081:Protein Array Analysis; D011485:Protein Binding; D020349:Surface Plasmon Resonance
chemical_list: D008024:Ligands; D009930:Organic Chemicals; D010455:Peptides; D015942:Factor VIIa