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Identification and X‐ray Co‐crystal Structure of a Small‐Molecule Activator of LFA‐1‐ICAM‐1 Binding
Author(s) -
Hintersteiner Martin,
Kallen Jörg,
Schmied Mario,
Graf Christine,
Jung Thomas,
Mudd Gemma,
Shave Steven,
Gstach Hubert,
Auer Manfred
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201310240
Subject(s) - activator (genetics) , small molecule , molecule , icam 1 , enhancer , chemistry , binding site , computational biology , biology , biochemistry , transcription factor , receptor , intracellular , organic chemistry , gene
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.