| Abstract: | The structure of cyclic antagonists of luteinizing hormone-releasing hormone (LHRH), Ac-D-Phe(p-Cl)1-D-Phe(p-C1)2-Trp3-Ser4-c(Asp5-D-Arg6-Leu7-Lys8)-Pro9-D-Ala10-NH2 ( I ), Ac-D-Phe(p-Cl)l-D-Phe(p-Cl)2-D-Trp3-Ser4-c(Glu5-Arg6-Leu7-Lys8)-Pro9-D-Ala10-NH2 ( II ) and their linear analogues, Ac-D-Phe(p-Cl)1-Phe(p-C1)2-Trp3-Ser4-Asp5-D-Arg6-Leu7-Lys8-Pro9-D-Ala10-NH2 ( III ) and Ac-D-Phe(p-Cl)1-D-Phe(p-C1)2-Trp3-Ser4-Glu5-D-Arg6-Leu7-Lys8-Pro9-D-Ala10-NH2 ( IV ), have been studied by NMR spectroscopy. The cyclic peptides I and II are more potent antagonists than the corresponding linear peptides in an in vivo assay. All the peptides show propensity of an unusual type II′β-turn involving residues 3–6. Cyclic analogues also show some additional structure around residues 7 and 8 which is absent in the linear peptides. This additional structure in the cyclic peptides may be due to a minor conformation with a β-turn between residues 5 and 8. © Munksgaurd 1995. |
