Conformational properties of gastrin fragments of increasing chain length

✍ Scribed by E. Peggion; M. T. Foffani; E. Wünsch; L. Moroder; G. Borin; M. Goodman; S. Mammi

• Publisher: Wiley (John Wiley & Sons)
• Year: 1985
• Tongue: English
• Weight: 956 KB
• Volume: 24
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360240406

✦ Synopsis

The conformational properties of a series of biologically active gastrin peptides of increasing chain length have been investigated in TFE solution by spectroscopic techniques. It was found that elongation of the glutamic acid sequence from 1 to 5 residues at the N-terminal portion of the molecules causes a cooperative change of the conformation of the peptide backbone. The environment of the biologically important C-terminal sequence -Trp-Nle-Asp-Phe-NH, monitored by the near-uv chiroptical properties is also affected by chain elongation. However, the change of the structure of the Cterminal portion does not parallel the conformational change of the peptide backbone. In fact, the final folded structure at the C-terminus is almost reached in the fragment with a sequence of 4 glutamic acid residues, while an additional, relevant conformational change of the backbone is observed on further elongation of the chain to minigastrin and little gastrin. The ability of the fragments to fold into a n ordered conformation on chain elongation parallels the increase of biological potency tested in vivo, reported in the literature, and suggests a correlation between these two facts. Ionization of the carboxyl side chains is without effect on the structure of the fragments with 2, 3, and 4 glutamic acid residues, while an effect is observed in minigastrin and little gastrin. From analysis of the CD properties and from their dependence upon side-chain ionization a structural model is proposed for the hormones minigastrin and little gastrin. This tentative model includes a P-bend located in the sequence Ala-Tyr-Gly-Trp and a short helical section at the N-terminal portion of the hormones.