Conformational studies on bombesin antagonists: CD and NMR characterization of [Thr6, Leu13 psi(CH2NH) Met14] bombesin (6-14).
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.
Di Bello
C
C
Institute of Industrial Chemistry, University of Padova, Italy.
Scatturin
A
A
Vertuani
G
G
D'Auria
G
G
Gargiulo
M
M
Paolillo
L
L
Trivellone
E
E
Gozzini
L
L
De Castiglione
R
R
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
D009842:Oligopeptides; D010446:Peptide Fragments; C074853:bombesin (6-14), Thr(6)-Leu(13)-psi(CH2NH)-Met(14)-; D001839:Bombesin