Structure-Activity Relationship of RGD-Containing Cyclic Octapeptide and αvβ3 Integrin Allows for Rapid Identification of a New Peptide Antagonist.

ABSTRACT: The αvβ3 integrin, a receptor for many extracellular matrix proteins with RGD-sequence motif, is involved in multiple physiological processes and highly expressed in tumor cells, therefore making it a target for cancer therapy and tumor imaging. Several RGD-containing cyclic octapeptide (named LXW analogs) were screened as αvβ3 antagonists with dramatically different binding affinity, and their structure-activity relationship (SAR) remains elusive. We performed systematic SAR studies and optimized LXW analogs to improve antagonistic potency. The NMR structure of LXW64 was determined and docked to the integrin. Structural comparison and docking studies suggested that the hydrophobicity and aromaticity of the X7 amino acid are highly important for LXW analogs binding to the integrin, a poten

SUBMITTER: Silva A 

PROVIDER: S-EPMC7246635 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature