The Last Advances on Solid-Phase Peptide Synthesis and NMR New Methodologies Applied to Cyclotides from Brazilian Plant Species

Abstract

Brazil is the nation with the largest biodiversity in the world accounting for more than 15% of all living species in the planet. This biodiversity represents a wide chemical and biological diversities, a universe of opportunities for scientific studies on chemistry of natural products and also biologically active compounds, with potential to support bio-based innovation. Thus, the current project is focused on peptides, one important class of natural products, which has been unexplored from our species. Peptides are defined as the short sequences of amino acids linked via either peptide bonds. They differ from proteins only on the basis of the number of residues, typically less than 50, while those shorter than 20 residues, tend to be labeled as oligopeptides. Among peptides, cyclotides are ribosomally synthesized cysteine-rich miniproteins, characterized by a head-to-tail cyclized backbone and three conserved disulfide-bonds in a knotted arrangement having a range of 28-37 amino acids, and combine a range of sequences in their six backbone loops between the conserved Cys residues. These are the focus of this project, which are aimed at isolation, structure elucidation, synthesis and some biologically bioassays of cyclotides accumulated the Brazilian Rubiaceae plant species Psychotria leiocarpa and Palicourea sessilis (syn. Psychotria longipes, Psychotria vellosiana). Modern NMR methods for macromolecules will be useful to this study. Additionally, total synthesis of five cyclotides already isolated from these species is in our objectives.