Solvent and temperature can affect the structural properties of cyclic peptides by controlling their flexibility. Here, we investigate two cyclic peptides, featuring beta turns. Using temperature-dependent NMR and FT-IR, we observed a pronounced temperature effect on the conformation of the cyclic peptide D-1 in CHCl3 but a much smaller effect in CH3 CN. Almost no effect was observed for its diastereomer L-1 within a similar temperature range and using the same solvents. With the aid of Replica Exchange Molecular Dynamics simulations and Quantum Mechanics/Molecular Mechanics calculations, we were able to explain this behavior based on the increased flexibility of D-1 (in CHCl3 ) in terms of intramolecular hydrogen bonding. The largest temperature dependence is observed for D-1 in CHCl3 , while the temperature effect is less pronounced for L-1 in CHCl3 and for both peptides in CH3 CN. This work provides new insights into the role of the environment and temperature on the conformations of cyclic peptides.
Keywords: IR spectroscopy; NMR spectroscopy; Quantum Mechanics/Molecular Mechanics; Replica Exchange Molecular Dynamics; cyclic peptides.
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