NMR studies on the structure of some cyclic and linear antagonists of luteinizing hormone-releasing hormone (LHRH).
The structure of cyclic antagonists of luteinizing hormone-releasing hormone (LHRH), Ac-D-Phe(p-Cl)1-D-Phe(p-Cl)2-D-Trp3-Ser4-c(Asp5-D-Arg6-Leu7- Lys8)-Pro9- D-Ala10-NH2 (I), Ac-D-Phe(p-Cl)1-D-Phe(p-Cl)2-D-Trp3-Ser4-c(Glu5-D-Arg6-Leu7- Lys8)-Pro9-D-Ala10-NH2 (II) and their linear analogues, Ac-D-Phe(p-Cl)1-D- Phe(p-Cl)2-D-Trp3-Ser4-Asp5-D-Arg6-Leu7-Lys8-Pro9-D-++ +Ala10-NH2 (III) and Ac-D-Phe(p-Cl)1-D-Phe(p-Cl)2-D-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' beta-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 beta-turn between residues 5 and 8.
Reddy
D V
DV
Indian Institute of Chemical Technology, Hyderabad.
Jagannadh
B
B
Dutta
A S
AS
Kunwar
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006727:Hormone Antagonists / Q000737:chemistry* / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010060:Ovulation / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats
D006727:Hormone Antagonists; D010455:Peptides; D010456:Peptides, Cyclic; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone