NMR-STUDIES ON THE STRUCTURE OF SOME CYCLIC AND LINEAR ANTAGONISTS OFLUTEINIZING-HORMONE-RELEASING HORMONE (LHRH)

The structure of cyclic antagonists of luteinizing hormone-releasing h ormone (LHRH), sp(5)-D-Arg(6)-Leu(7)-Lys(8))-Pro(9)-D-Ala(10)-NH2 (I), lu(5)-D-Arg(6)-Leu(7)-Lys(8))-Pro(9)-D-Ala(10)-NH2 (II) and their lin ear analogues, Asp(5)-D-Arg(6)-Leu(7)-Lys(8)-Pro(9)-D-Ala(10)-NH2 (III ) and Glu(5)-D-Arg(6)-Leu(7)-Lys(8)-Pro(9)-D-Ala(10)-NH2 (IV), have be en studied by NMR spectroscopy. The cyclic peptides I and II are more potent antagonists than the corresponding linear peptides in an in viv o assay. All the peptides show propensity of an unusual type II' beta- turn involving residues 3-6. Cyclic analogues also show some additiona l structure around residues 7 and 8 which is absent in the linear pept ides. This additional structure in the cyclic peptides may be due to a minor conformation with a beta-turn between residues 5 and 8. (C) Mun ksgaard 1995.