NMR AND QUENCHED MOLECULAR-DYNAMICS STUDIES OF SUPERPOTENT LINEAR ANDCYCLIC ALPHA-MELANOTROPINS

Conformational searching, computer simulations, synthesis and NMR are used on a variety of alpha melanocyte-stimulating hormone (alpha-MSH) analogues to understand the physical characteristics required for biol ogical potency. Peptides le(4),Asp(5),D-Phe(7),Lys(10)]alpha-MSH(4-10) -NH2) and III Nle(4),Asp(5),D-Phe(7),Dap(10)]alpha-MSH(4-10)-NH2 all s how very similar conformational properties (backbone and side-chain to rsional angles), and all display high biological potencies. The modeli ng results for these compounds are supported by the NMR data. Peptide IV c-c[Nle(4),Asp(5),D-Phe(7),Dap(10)]alpha-MSH(4-10) appears to have a markedly different conformation and has decreased biological potency . (C) Munksgaard 1998.