Effects of C alpha-methyl substitution on the conformation of linear GnRH antagonist analogs.
We have examined the effect of C alpha-methyl groups on the conformational ensemble of GnRH analog peptides by comparing 1H 2D NMR data from two analogs, Ac-D-Nal1-D-4-Cl-C alpha-Me-Phe2-D-Pal3-Ser4-Tyr5-D-Arg6-Leu7-Arg8-Pro9-D-Al a10- NH2 (1) and Ac-D-Nal1-D-4-Cl-C alpha-Me-Phe2-D-Pal3-Ser4-C alpha-Me-Tyr5-D-Arg6- Leu7-C alpha-Me-Arg8-Pro9-D-Ala10-NH2 (2). The two additional C alpha-methyl groups in residues 5 and 8 of 2 do not influence significantly the pattern of the observable main chain NOE intensities, or of the backbone HN proton chemical shifts, which indicates that they do not produce global changes in the conformational ensemble of the peptide. A local change induced by the substitution was observed in the conformation at D-Arg8-Pro9.
Liff
M I
MI
Philadelphia College of Textiles and Science, Pennsylvania.
Kopple
K D
KD
Tian
Z
Z
Roeske
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008745:Methylation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D010902:Pituitary Gland / Q000378:metabolism / Q000648:ultrastructure; D011487:Protein Conformation; D051381:Rats; D011966:Receptors, LHRH / Q000378:metabolism
D009842:Oligopeptides; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone