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

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.