Structure-activity relationship studies of a series of peptidomimetic ligands for alpha(4) beta(1) integrin on Jurkat T-leukemia cells |
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Authors: | Liu Ruiwu Peng Li Han Huijun Lam Kit S |
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Institution: | Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Cancer Center, University of California Davis, 4501 X Street, Sacramento, CA 95817, USA. rwliu@ucdavis.edu |
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Abstract: | alpha(4)beta(1) integrin is a therapeutic target for inflammation, autoimmune diseases, and lymphoid cancers. A series of peptidomimetic ligands based on the Nle-D-I motif have been synthesized and their binding affinities (IC(50)) to activated alpha(4)beta(1) integrin on Jurkat T-leukemia cells have been determined using a cell adhesion assay. One of the 51 ligands, 18, has been determined to have an IC(50) of 0.6 nM and has a more than twofold increase of binding affinity than the initial lead compound 1. Extensive SAR studies provide important information for further ligand optimization, which has served as a foundation for studies that ultimately led to identification of a potent ligand with an IC(50) of 2 pM. |
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