Conformational studies on bombesin antagonists: CD and NMR characterization of [Thr 6 , Leu 13 ψ(CH 2 NH) Met 14 ] bombesin (6–14)
1991; Wiley; Volume: 31; Issue: 12 Linguagem: Inglês
10.1002/bip.360311206
ISSN1097-0282
AutoresCarlo Di Bello, Angelo Scatturin, Gianni Vertuani, Gabriella D’Auria, Mario Gargiulo, Livio Paolillo, E. Trivellone, Luigia Gozzini, Roberto Castiglione,
Tópico(s)Neuropeptides and Animal Physiology
ResumoAbstract 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.
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