RATIONAL DESIGN OF POHLIANIN A ORBITIDES ANALOGUES USING D AND L-AMINO ACIDS FOR CONFORMATIONAL STUDIES VIA VIBRATIONAL CIRCULAR DICHROISM (VCD)

The peptide Pohlianin A, a bioactive head-to-tail natural cyclic peptide belonging to an orbitides’ group from Jatropha, and which has biological properties, since this class has promising development in the pharmacological area. Pohlianin A has some relevant features that maintain its structure, like the residue pairs Tyr₇–Pro₁ and Val₄–Leu₅. Therefore, to study the conformational restrictions of these parameters and, consequently, their conformational result for the planned analogues, these amino acids were replaced by their D-enantiomers. Studies using amino acids L and D replace key residues important for the conformation of Pohlianin A and are essential to analyze its three-dimensional modifications to understand how this modification will affect the synthesis product. In this way, the stereochemical characteristics of these linear and cyclic peptides of plant origin were studied, and the potentialities and limitations of chiroptical methods were investigated as a self-probe for the absolute configuration and conformations of plant peptides, without the need for their hydrolysis. To this end, specific modifications were made to the primary sequence of the Pohlianin A orbitide, replacing some L-amino acids with their D-enantiomers via Solid Phase Peptide Synthesis. Initial characterization was also carried out using High Performance Liquid Chromatography (HPLC) and Mass Spectrometry techniques. Initially, peptide analogue syntheses were carried out by replacing the pairs Tyr₇–Pro₁ and Val₄–Leu₅ pair by their D-enantiomeric residues. After synthesis, the Vibrational Circular Dichroism (VCD) technique was used. With the peptide synthesis carried out, it was possible to successfully obtain Pohlianin A analogues with its enantiomeric structural modifications. After that, the molecules were evaluated by VCD method, which was carried out to gather correct identification of the peptides through its analyses, proving to be an interesting biophysical technique for analysis, conformation and compilation of natural products enantiomers.