Abstract
α4β1 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 (IC50) to activated α 4β1 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 IC50 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 IC50 of 2 pM.
Original language | English (US) |
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Pages (from-to) | 595-604 |
Number of pages | 10 |
Journal | Biopolymers - Peptide Science Section |
Volume | 84 |
Issue number | 6 |
DOIs | |
State | Published - 2006 |
Keywords
- αβ integrin
- Cell adhesion assay
- Jurkat T-leukemia cells
- Peptidomimetic ligand
- SAR study
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biophysics