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

Olga Ovdiichuk (1, 2) , Olga Hordiyenko (2) , Evgenia Fotou (1) , Caroline Gaucher (3) , Axelle Arrault (1) , Marie-Christine Averlant-Petit (1)

1 LCPM - Laboratoire de Chimie Physique Macromoléculaire
2 Taras Shevchenko National University of Kyiv
3 CITHEFOR - Cibles thérapeutiques, formulation et expertise pré-clinique du médicament

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 intramolec- ular hydrogen bonding including a seven-membered γ-turn formation. In addition, a cis/trans equilibrium study was pres- ent for prolyl amides in polar solvents (D2O and DMSO). A phenylalanine substituent was found to exhibit profound ef- fect on thermodynamic parameters in prolyl peptides. The presence of intramolecular hydrogen bonds dramatically in- creases 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 cy- totoxic therefore they can be further studied in relation to potent biological activities.

Mots clés: NMR spectroscopy; FT-IR spectroscopy; Cytocompatibility; Molecular dynamics; Amidoxime

Domaines: Chimie; Chimie thérapeutique

Olga Ovdiichuk, Olga Hordiyenko, Evgenia Fotou, Caroline Gaucher, Axelle Arrault, et al.. Conformational studies of new pseudotripeptide with pyrazine amidoxime motif and simplified analogs using IR, NMR spectroscopy, and molecular dynamic simulations. Structural Chemistry, 2017, 28 (3), pp.813-822. ⟨10.1007/s11224-016-0870-2⟩. ⟨hal-01627739⟩