Peptide Analogues Containing β-Amino Acids for the Melanocortin System

The melanocortin system is a complex control center that regulates various physiological pathways, which include skin pigmentation, steroidogenesis, sexual function, sebaceous lipid production, energy and weight homeostasis, and food satiety. [1,2] This system consists of five G-protein coupled receptors (MC1R-MC5R), four known endogenous agonists, and two known endogenous antagonists. [2, 3] The endogenous agonists of the melanocortin system are α-, ß-, and γmelanocytestimulating hormones (α-, ß-, γ-MSH) and adrenocorticotropin hormone (ACTH). All four of these endogenous agonist ligands are derived from the posttranslational processing of the proopicomelanocortin (POMC) gene. [4,5] These hormones bind to the melanocortin receptors and activate the cyclic adenosine monophosphate (cAMP) signal transduction pathway, which generates a cascade of intracellular reactions that result in a physiological response. [6] The endogenous antagonists are Agouti and Agouti-related protein AgRP. [7,