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Conformational studies of new pseudotripeptide with pyrazine amidoxime motif and simplified analogs using IR, NMR spectroscopy, and molecular dynamic simulations

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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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Authors and Affiliations

  1. Laboratoire de Chimie Physique Macromoléculaire, UMR7375 CNRS Université de Lorraine, 1 rue Grandville, BP 20451, 54001, Nancy, France

    Olga Ovdiichuk, Evgenia Fotou, Axelle Arrault & Marie-Christine Averlant-Petit

  2. Chemistry Department, Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska str, Kyiv, 01601, Ukraine

    Olga Ovdiichuk & Olga Hordiyenko

  3. CITHEFOR, EA3452, Faculté de Pharmacie, Université de Lorraine, 5 rue Albert Lebrun, BP 80403, 54001, Nancy, France

    Caroline Gaucher

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  1. Olga Ovdiichuk
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  2. Olga Hordiyenko
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  3. Evgenia Fotou
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  4. Caroline Gaucher
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  5. Axelle Arrault
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  6. Marie-Christine Averlant-Petit
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Correspondence to Marie-Christine Averlant-Petit.

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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

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