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Evidence of Complete Hydrophobic Coating of Bombesin by Trifluoroethanol in Aqueous Solution: An NMR Spectroscopic and Molecular Dynamics Study

2002; Wiley; Volume: 8; Issue: 7 Linguagem: Inglês

10.1002/1521-3765(20020402)8

1521-3765

Dolores Díaz, Marco Fioroni, Klaus Burger, Stefan Berger,

Spectroscopy and Quantum Chemical Studies

Bombesin is a tetradecapeptide that possesses a random coil structure in pure water. In the presence of 30 % (v/v) 2,2,2-trifluoroethanol (TFE), it adopts a partial helical conformation involving the C-terminal amino acids 6–14. This conformational change, known as the TFE effect, is studied here in terms of the solvation state of the peptide at different TFE concentrations by means of intermolecular homo- and heteronuclear NOE measurements. When an aqueous solution of bombesin is titrated with TFE, a continual decrease in the water/peptide interactions and a concomitant increase in the TFE/peptide interactions is observed, and at 30 % (v/v) TFE no homonuclear NOEs between water and the peptide can be detected. The conformational transition of the bombesin molecule is thus accompanied by a complete surface covering with TFE. A parallel molecular dynamics (MD) study of the peptide in aqueous solution with the single-point charge (SPC) water model and in a 30 % (v/v) TFE/water mixture with a recently developed TFE model has also been performed. The 10 ns simulations were in agreement with the experimental data. The calculations indicate stabilisation of the α-helix in the H2O/TFE mixture, in contrast to the situation in pure water, and clustering of the TFE molecules around the peptide.