Structural Chemistry

, Volume 28, Issue 3, pp 813–822 | Cite as

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

  • Olga Ovdiichuk
  • Olga Hordiyenko
  • Evgenia Fotou
  • Caroline Gaucher
  • Axelle Arrault
  • Marie-Christine Averlant-Petit
Original Research
  • 137 Downloads

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.

Keywords

Amidoxime FT-IR spectroscopy NMR spectroscopy Molecular dynamics Cytocompatibility 

Notes

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.

Supplementary material

11224_2016_870_MOESM1_ESM.docx (7.5 mb)
ESM 1 (DOCX 7725 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Laboratoire de Chimie Physique MacromoléculaireUMR7375 CNRS Université de LorraineNancyFrance
  2. 2.Chemistry DepartmentTaras Shevchenko National University of KyivKyivUkraine
  3. 3.CITHEFOR, EA3452, Faculté de PharmacieUniversité de LorraineNancyFrance

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