1609659-33-7Relevant academic research and scientific papers
Identification and X-ray Co-crystal structure of a small-molecule activator of LFA-1-ICAM-1 binding
Hintersteiner, Martin,Kallen, Joerg,Schmied, Mario,Graf, Christine,Jung, Thomas,Mudd, Gemma,Shave, Steven,Gstach, Hubert,Auer, Manfred
supporting information, p. 4322 - 4326 (2014/05/06)
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. Tuned up: The LFA-1 ICAM-1 interaction is a fundamental step in T-cell activation in response to antigen encounter. A small-molecule activator of LFA-1, IBE-667, was identified by confocal on-bead screening. The identified activator binds to LFA-1 I domain, as revealed by the co-crystal structure, and increases the affinity of LFA-1 for ICAM-1 on activated T-cells.
