The integrin receptors represent valuable targets for therapeutic interventions; being overexpressed
in many pathological states, their inhibition can be effective to treat a number of severe diseases.
Since integrin functions are mediated by interactions with ECM protein ligands, the inhibition
can be achieved by interfering with such interactions using small mimetics of the integrin-ligand recognition
motifs (e.g. RGD, LDV, etc.). In this review, we focus on the antagonists with peptideheterocycle
hybrid structures. The introduction of well-designed scaffolds has met considerable success
in the rational design of highly stable, bioavailable, and conformationally defined antagonists.
Two main approaches are discussed herein. The first approach is the use of scaffolds external to the
main recognition motifs, aimed at improving conformational definition. In the second approach, heterocyclic cores are introduced
within the recognition motifs, giving access to libraries of 3D diverse candidate antagonists.