Synthesis of cyclic peptides with binding affinity for MC-4 receptor

摘要

The melanocortin receptors(MC-1 R to-5R)are involved in a wide range of physiological functions.The endogenous MC-Rs agonists ACTH and alpha-MSH contain a common sequence,His-Phe-Arg-Trp,which is an essential core for their biological activities Bednarek et al.reported that cyclo(CO-CH_2-CH_2-CO-His-D-Phe-Arg-Trp-Dab)-NH_2(Dab=2,4-diaminobutyric acid)exhibited a potent agonist activity at hMC-4R.Our aim is to examine the ring size-binding affinity relationship of cyclic peptides,and extend that structure to the design of non-peptide agonist for MC-4R,which plays an important role in body weight regulation and energy homeostasis.In this study,we deal with the synthesis of cyclo(His-D-Phe-Arg-Trp-Z)(Z=omega-amino acid)and their binding affinities at MC-R4.