Cyclic peptides from brazilian plants: isolation, structural characterization, synthesis, and evaluation of biological activities

• Grant number: 19/26550-3
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): April 01, 2020
• Effective date (End): March 11, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal researcher: Mario Sergio Palma
• Grantee: Antonio Fernández Bobey
• Home Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil
• Associated research grant: 16/16212-5 - Natural proteopeptides from the Brazilian fauna, flora and microbiota as potential models for the rational development of new drugs of therapeutic use: isolation, structure elucidation, chemical synthesis and functional activity assays, AP.BTA.TEM

Abstract

Some taxons of angiosperms biosynthesize peculiar substances known as cyclotides. Research about this class of natural products in species of Brazilian biodiversity is a theme of cutting-edge scientific research, with few Brazilian research groups in this area. Cyclotideshave potent insecticidal, anthelmintic and molluscicidal activities, what makes believe thatits biological function is related to plant defense, and makes them potential candidates for application in Agriculture. In addition, considering the importance of Agribusiness in the Brazilian economy, as well as the excessive use of pesticides, harmful to human health and the environment, which it uses, studying this class of molecules would be extremely promising. In this project, in a first phase, we proposed the prospection, identification, isolation and characterization of cyclotides in Brazilian species of Violaceae family, for this purpose, advanced chromatographic techniques will be employed (MPLC-PDA, HPLC-PDA,UHPLC-PDA-MS) and characterization techniques (mono and two-dimensional Nuclear Magnetic Resonance, MALDI-TOF/TOF Mass Spectrometry, LC-ESI-MS/MS and amino acidanalysis). In a second phase, Solid Phase Peptide Synthesis (SPPS) of the natural cyclotides obtained will be performed, using Fmoc/tBU methodology, as well as their redesign in order to enhance insecticide activity against crop pest of commercial interest and decrease toxicity (in vitro cytotoxicity assays). (AU)