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