Diverse ring architectures of cyclic peptidomimetics targeting melanocortin receptors.

Abstract

The melanocortin receptor (MCR) family consists of five G protein-coupled receptors (MC1R-MC5R) that are activated by peptide hormones α, β and γ-MSH and ACTH. These receptors are involved in diverse physiological and pathological processes and have been the target of therapeutic development, including approved drugs. In this review, we look at the way in which cyclic peptides have been developed that target the MC1R, MC3R, MC4R and MC5R receptors, from the well-studied side-chain lactam-bridged and disulphide-linked macrocycles, through to less conventional architectures and linkage chemistries. We show that there is a historical gap in the evaluation of these architectures in terms of their influence upon potency, selectivity and pharmacokinetics.