@article {546736, title = {Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.}, journal = {Bioorg Med Chem. }, volume = {22}, number = {7}, year = {2014}, pages = {2353-65}, abstract = { The inhibition of\ protein-protein\ interactions remains a challenge for traditional small molecule drug\ discovery. Here we describe the use of DNA-encoded\ library\ technology\ for the\ discovery\ of small molecules that are\ potent\ inhibitors of the\ interaction\ betweenlymphocyte\ function-associated\ antigen\ 1\ and its ligand intercellular adhesion molecule\ 1. A DNA-encoded\ library\ with a potential complexity of 4.1\ billion compounds was exposed to the I-domain of the\ target\ protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the\ lymphocyte\ function-associated\ antigen\ 1/intercellular adhesion molecule-1\ interaction\ with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the\ target\ protein. Copyright {\textcopyright} 2014 Elsevier Ltd. All rights reserved. }, author = {Kollman, CS and Bai, X and Tsai, CH and Yang, H and Lind, KE and Skinner, SR and Zhu, Z. and Israel, DI and Cuozzo, JW and Morgan, BA and Yuki, K and Xie, C. and Springer, T.A. and Shimaoka, M. and Evindar, G} }