title: Identification and X-ray co-crystal structure of a small-molecule activator of LFA-1-ICAM-1 binding.
abstract: Stabilization of protein-protein interactions by small molecules is a concept with few examples reported to date. Herein we describe the identification and X-ray co-crystal structure determination of IBE-667, an ICAM-1 binding enhancer for LFA-1. IBE-667 was designed based on the SAR information obtained from an on-bead screen of tagged one-bead one-compound combinatorial libraries by confocal nanoscanning and bead picking (CONA). Cellular assays demonstrate the activity of IBE-667 in promoting the binding of LFA-1 on activated immune cells to ICAM-1.
authors.affiliation: Bioseutica BV, Corso Elvezia 4, 6900 Lugano (Switzerland). MHintersteiner@bioseutica.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Hintersteiner
authors.forename: Jörg
authors.initials: J
authors.lastname: Kallen
authors.forename: Mario
authors.initials: M
authors.lastname: Schmied
authors.forename: Christine
authors.initials: C
authors.lastname: Graf
authors.forename: Thomas
authors.initials: T
authors.lastname: Jung
authors.forename: Gemma
authors.initials: G
authors.lastname: Mudd
authors.forename: Steven
authors.initials: S
authors.lastname: Shave
authors.forename: Hubert
authors.initials: H
authors.lastname: Gstach
authors.forename: Manfred
authors.initials: M
authors.lastname: Auer
mesh_terms: D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D057166:High-Throughput Screening Assays; D006801:Humans; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001381:Azepines; C000596853:IBE-667; D007191:Indazoles; D016169:Lymphocyte Function-Associated Antigen-1; D054852:Small Molecule Libraries; D018799:Intercellular Adhesion Molecule-1
keywords: LFA-1; OBOC libraries; high-throughput screening; small-molecule activators; structural biology