Abstract
Solution structures of new pyrazine-based pseudotripeptide with amidoxime function and simplified pseudodipeptide analogs were determined by a combination of IR and NMR spectroscopic studies and molecular dynamic simulations using explicit chloroform as a solvent. It was found that proline-phenylalanine dipeptide residue and amidoxime moiety in o-position are essential for intramolecular hydrogen bonding including a seven-membered γ-turn formation. In addition, a cis/trans equilibrium study was present for prolyl amides in polar solvents (D2O and DMSO). A phenylalanine substituent was found to exhibit profound effect on thermodynamic parameters in prolyl peptides. The presence of intramolecular hydrogen bonds dramatically increases the amount of trans isomer in non-hydrogen-bonding CHCl3 and significantly favor cis isomer in hydrogen-bonding solvents such as DMSO and D2O. All molecules are not cytotoxic therefore they can be further studied in relation to potent biological activities.
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Acknowledgements
The authors thank the NMR facilities SCBIM (Service Commun de Bioingénierie Moléculaire, Cellulaire et Thérapeutique), FR3209 CNRS-UL of Université de Lorraine, and X-Ray diffraction facilities of Université de Lorraine. We also thank Isabelle FRIES for cytocompatibility tests and to Olivier FABRE for NMR analysis and Emmanuel Wenger for XRD experiments.
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Ovdiichuk, O., Hordiyenko, O., Fotou, E. et al. Conformational studies of new pseudotripeptide with pyrazine amidoxime motif and simplified analogs using IR, NMR spectroscopy, and molecular dynamic simulations. Struct Chem 28, 813–822 (2017). https://doi.org/10.1007/s11224-016-0870-2
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DOI: https://doi.org/10.1007/s11224-016-0870-2