title: Hydrophobically induced conformation in ovine corticotropin-releasing hormone.
abstract: Multiple peptide synthesis has been applied for the simultaneous synthesis of systematic replacement sets of model peptides which varied in length from 18 to 36 residues and ovine corticotropin-releasing hormone (oCRH), a 41-residue receptor-binding peptide. The peptides were utilized to analyze the capability of the stationary phase during RP-HPLC to induce secondary structure in long-chain linear peptides. Double D-amino acid replacement studies demonstrate that nonamphipathic helical domains can be recognized, even in the presence of highly amphipathic domains. On the other hand, systematic alteration of hydrophobicity at each residue along the sequence by methionine and methionine sulfoxide replacements results in characteristic pattern of HPLC retention-time differences, which is shown to provide a useful method to probe hydrophobic surface regions in helical peptides. Both amino acid replacement strategies were successfully applied to characterize the hydrophobically induced structure of oCRH. Although an alpha-helix is formed from residues 6 to 32, the N-terminal residues 1-5 and the C-terminal region 33-41 do not show any regular structure. The helical domain from residues 12 to 20 is highly amphipathic.
authors.affiliation: Institute of Molecular Pharmacology, Berlin, Germany. sven@pout.phol.cwru.edu
authors.forename: S
authors.initials: S
authors.lastname: Rothemund
authors.forename: E
authors.initials: E
authors.lastname: Krause
authors.forename: M
authors.initials: M
authors.lastname: Beyermann
authors.forename: M
authors.initials: M
authors.lastname: Bienert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012756:Sheep
chemical_list: D010455:Peptides; D003346:Corticotropin-Releasing Hormone; D008715:Methionine; C013111:methionine sulfoxide