Conformation-function relationships in LHRH analogs. I. Conformations of LHRH peptide backbone.
A systematic conformational build-up procedure was performed for the LHRH molecule, pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH 2. The results showed a very high flexibility of the LHRH backbone, with 300 conformers being regarded as having low energy. At the same time, the conformational flexibility of LHRH differs among the fragments of the molecule. The most rigid fragments of LHRH are the Ser4-Tyr5-Gly6-Leu7 and Tyr5-Gly6-Leu7-Arg8 central tetrapeptides, the latter possessing only eight different types of low-energy backbone conformers. These eight conformer types belong to different kinds of chain reversals which are stabilized by different systems of intramolecular hydrogen bonds. Some of them resemble the beta-II' turn, which was derived as the LHRH structure from energy calculations by others. The results obtained are in good agreement with the experimental data on LHRH flexibility in solution.
Nikiforovich
G V
GV
Center for Molecular Design, Washington University, St. Louis, Missouri.
Marshall
G R
GR
D000595:Amino Acid Sequence; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry*; D006860:Hydrogen Bonding; D008432:Mathematical Computing; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D007987:Gonadotropin-Releasing Hormone