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Conformational studies on bombesin antagonists: CD and NMR characterization of [Thr 6 , Leu 13 ψ(CH 2 NH) Met 14 ] bombesin (6–14)
Author(s) -
Di Bello Carlo,
Scatturin Angelo,
Vertuani Gianni,
D'Auria Gabriella,
Gargiulo Mario,
Paolillo Livio,
Trivellone Enrico,
Gozzini Luigia,
De Castiglione Roberto
Publication year - 1991
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360311206
Subject(s) - chemistry , random coil , bombesin , conformational isomerism , nmr spectra database , crystallography , aqueous solution , peptide , nuclear magnetic resonance spectroscopy , stereochemistry , resonance (particle physics) , spectral line , molecule , circular dichroism , organic chemistry , neuropeptide , receptor , biochemistry , physics , particle physics , astronomy
Abstract The conformational flexibility of the [Thr 6 , Leu 13 ψ(CH 2 NH) Met 14 ]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 –Phe 12 , Leu 14 ]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 m M SDS) for all three peptides, namely BN, [ D ‐Phe 12 , Leu 14 ]BN, and [Thr 6 , Leu 13 ψ(CH 2 NH)Met 14 ]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‐αCH 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.