MOLECULAR MODELING OF BETA-TURNS IN A CYCLIC MELANOTROPIN

alpha-Melanocyte stimulating hormone (alpha-MSH) is a tridecapeptide w hich interacts with a family of G protein-coupled receptors, the melan ocortin receptors, to cause its biological effects. We have modelled t he low energy conformations of the alpha-MSH derivatives as part of a project to probe the receptor binding conformation of melanocortins, a nd also to design ligands for targeting cytotoxic drugs to MC1 recepto rs expressed by melanoma cells. Here we report a molecular dynamics st udy of beta turns in a cyclic lactam analogue [Nle(4), Asp(5), D-Phe(7 ), Lys(10)]alpha-MSH. The data show that it is possible for a beta tur n to exist in the ring portion of this molecule which contains the mel anocortin conserved sequence -His-Phe-Arg-Trp-, even though the lowest energy conformers lack a beta turn.