Conformational studies on bombesin antagonists: CD and NMR characterization of [Thr6, Leu13ψ(CH2NH) Met14] bombesin (6–14)
✍ Scribed by Carlo Di Bello; Angelo Scatturin; Gianni Vertuani; Gabriella D'Auria; Mario Gargiulo; Livio Paolillo; Enrico Trivellone; Luigia Gozzini; Roberto De Castiglione
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1991
- Tongue
- English
- Weight
- 738 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
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.