title: Conformational studies on bombesin antagonists: CD and NMR characterization of [Thr6, Leu13 psi(CH2NH) Met14] bombesin (6-14).
abstract: The conformational flexibility of the [Thr6, Leu13 psi(CH2NH) Met14] bombesin (6-14) nonapeptide has been studied by CD and one- and two-dimensional (1D and 2D) nmr techniques. The CD and nmr parameters in different solvents and in a micellar environment (SDS) are compared with the data collected for the parent bombesin (BN) and [D-Phe12, Leu14]BN. A preliminary investigation on spantide is also reported. In particular, the results obtained from CD measurements indicate that there is a shift from random coil structures, in aqueous solutions, toward folded structures in apolar media (2,2,2-trifluoroethanol) and in a membrane-mimetic environment (40 mM SDS) for all three peptides, namely BN, [D-Phe12, Leu14]BN, and [Thr6, Leu13 psi(CH2NH) Met14]BN (6-14). Spantide, which also possesses some inhibitory activity against BN but very little sequence similarity, even in water, shows an ordered conformation. Nuclear magnetic resonance parameters such as backbone NH-alpha CH coupling constant values, amidic temperature coefficients, and the presence of only sequential nuclear Overhauser effects have not provided, so far, any clear evidence for a preferential ordered structure in the peptides studied, and this may be due to rapid exchange among different conformers in the nmr time scale.
authors.affiliation: Institute of Industrial Chemistry, University of Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Bello
authors.forename: A
authors.initials: A
authors.lastname: Scatturin
authors.forename: G
authors.initials: G
authors.lastname: Vertuani
authors.forename: G
authors.initials: G
authors.lastname: D'Auria
authors.forename: M
authors.initials: M
authors.lastname: Gargiulo
authors.forename: L
authors.initials: L
authors.lastname: Paolillo
authors.forename: E
authors.initials: E
authors.lastname: Trivellone
authors.forename: L
authors.initials: L
authors.lastname: Gozzini
authors.forename: R
authors.initials: R
authors.lastname: De Castiglione
mesh_terms: D000595:Amino Acid Sequence; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; C074853:bombesin (6-14), Thr(6)-Leu(13)-psi(CH2NH)-Met(14)-; D001839:Bombesin