Integrin Ligands with α/β-Hybrid Peptide Structure: Design, Bioactivity, and Conformational Aspects

Med Res Rev. 2016 May;36(3):389-424. doi: 10.1002/med.21383. Epub 2016 Jan 18.

Abstract

Integrins are cell surface receptors for proteins of the extracellular matrix and plasma-borne adhesive proteins. Their involvement in diverse pathologies prompted medicinal chemists to develop small-molecule antagonists, and very often such molecules are peptidomimetics designed on the basis of the short native ligand-integrin recognition motifs. This review deals with peptidomimetic integrin ligands composed of α- and β-amino acids. The roles exerted by the β-amino acid components are discussed in terms of biological activity, bioavailability, and selectivity. Special attention is paid to the synthetic accessibility and efficiency of conformationally constrained heterocyclic scaffolds incorporating α/β-amino acid span.

Keywords: cancer; heterocycle; integrin; peptidomimetic; β-amino acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Integrins / chemistry*
  • Ligands
  • Peptides / chemistry*
  • Protein Conformation

Substances

  • Integrins
  • Ligands
  • Peptides