Conformational and biological properties of the Ala10-analog of human Des-Trp1, Nle12-minigastrin

• Published in: Biochemistry (Easton) Vol. 28; no. 18; pp. 7182 - 7188
• Main Authors: Mammi, Stefano, Foffani, Maria Teresa, Peggion, Evaristo, Galleyrand, Jean Claude, Bali, Jean Pierre, Simonetti, Mario, Goehring, Walter, Moroder, Luis, Wuensch, Erich
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 05.09.1989
• Subjects: Alanine; Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Chemical Phenomena; Chemistry; Circular Dichroism; Fundamental and applied biological sciences. Psychology; Gastric Acid - metabolism; Gastrins - analysis; Gastrins - biosynthesis; Gastrins - metabolism; Gastrins - pharmacology; Humans; Magnetic Resonance Spectroscopy; Male; Protein Binding; Protein Conformation; Proteins; Rabbits; Rats; Temperature; Human; Analysis; Circular dichroism spectrometry; Gastrin; Peptide hormone; HPLC chromatography; Biosynthesis; NMR spectrometry; Biological activity; Conformation
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00444a008

Synthesis, conformation, and biological properties of the Ala10 analogue of des-Trp1,Nle12-minigastrin are reported. Replacement of the Gly residue in the original sequence with Ala remarkably changes the conformational preference of the hormone in trifluoroethanol. CD and NMR results indicate that the conformational change is mainly located in the C-terminal portion of the molecule, with probable extension of the N-terminal alpha-helix throughout the entire sequence. The structural modification causes a 10-fold decrease in the biological potency of the hormone, which is about as active as the C-terminal tetrapeptide amide. These findings support our previous hypothesis that the optimal bioactive conformation of the native hormone is U-shaped, with mutual interactions among the two end segments.