Affinity-Guided Design of Caveolin-1 Ligands for Deoligomerization

  • J Med Chem. 2016 Apr 28;59(8):4019-25. doi: 10.1021/acs.jmedchem.5b01536.
Amanda J H Gilliam  1 ,  Joshua N Smith  1 ,  Dylan Flather  1 ,  Kevin M Johnston  1 ,  Andrew M Gansmiller  1 ,  Dmitry A Fishman  1 ,  Joshua M Edgar  1 ,  Mark Balk  1 ,  Sudipta Majumdar  1 ,  Gregory A Weiss  1
Affiliations
  • 1. Department of Chemistry, and ‡Department of Molecular Biology and Biochemistry, University of California , Irvine, California 92697-2025, United States.
PMID: 27010220 DOI: 10.1021/acs.jmedchem.5b01536
Abstract

Caveolin-1 is a target for academic and pharmaceutical research due to its many cellular roles and associated diseases. We report peptide WL47 (1), a small, high-affinity, selective disrupter of caveolin-1 oligomers. Developed and optimized through screening and analysis of synthetic peptide libraries, ligand 1 has 7500-fold improved affinity compared to its T20 parent ligand and an 80% decrease in sequence length. Ligand 1 will permit targeted study of caveolin-1 function.

Products