Design of new small, cyclic melanocortin receptor-binding peptides using molecular modelling: Role of the His residue in the melanocortin peptide core

The conserved core of melanocyte stimulating hormones (MSH), His-Phe-Arg-Tr p, was probed by comparing a cyclic pentapeptide containing His-DPhe-Arg-Tr p, with three structurally similar cyclic peptides, that lacked the His res idue. All three peptides bound to the MG,, MG,, MC, and MC, receptors with similar affinities. Molecular modelling indicated that the 3D structure of the DPhe-Arg-Trp of all three peptides were closely similar. The data indic ate that the His residue of the small rigid cyclic MSH core peptides does n ot participate in binding with the melanocortin receptors. (C) 2001 Edition s scientifiques et medicales Elsevier SAS.