Approaches to cyclic peptide beta-turn mimics

The beta -turn is a common recognition feature between peptide ligands and their macromolecular targets. The cyclization of a short peptide segment wi th a linker is one method of imitating this conformation. The first part of this review discusses tethering strategies which have resulted in the deve lopment of mimetics for the enkephalins and somatostatin as well as in the discovery of antagonists for targets such as thrombin, the CD4 protein on T lymphocytes, the integrins, and other receptors involved in inflammatory d iseases. The second portion of this review describes the application of ami nocaproic acid (Aca) as a tether in cyclic peptide beta -turn mimics. Alkyl substituents on Aca may influence the beta -turn preference of the dipepti de. The synthesis of the substituted Aca linkers and their incorporation in to the macrocycles is highlighted.