Identification and X-ray Co-crystal Structure of a Small-Molecule Activator of LFA-1-ICAM-1 Binding

Martin Hintersteiner, Joerg Kallen, Mario Schmied, Christine Graf, Thomas Jung, Gemma Mudd, Steven Shave, Hubert Gstach, Manfred Auer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4322-4326
Number of pages5
JournalAngewandte Chemie International Edition
Volume53
Issue number17
DOIs
Publication statusPublished - 22 Apr 2014

Keywords

  • high-throughput screening
  • LFA-1
  • OBOC libraries
  • small-molecule activators
  • structural biology
  • function-associated antigen-1
  • one-compound libraries
  • I-domain
  • thrombopoietin receptor
  • conformatiotional-changes
  • LFA-1 inhibition
  • cell adhesion
  • integrin
  • agonist
  • lymphocytes

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