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

• Grant number: 19/04381-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 01, 2019
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Eduardo Maffud Cilli
• Grantee: Meri Emili Pinto Nascimento
• Supervisor: David Craik
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Queensland, Brisbane (UQ), Australia
• Associated to the scholarship: 17/17098-4 - Application of MALDI Imaging (MSI) on non-nodulated and nodulated leaves of Psychotria and Hybanthus: Localization, analysis of cyclotides and its relationship with endosymbionts bacteria, BP.PD

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.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINTO, MERI EMILI F.; CHAN, LAI YUE; KOEHBACH, JOHANNES; DEVI, SEEMA; GRUNDEMANN, CARSTEN; GRUBER, CHRISTIAN W.; GOMES, MARIO; BOLZANI, VANDERLAN S.; CILLI, EDUARDO MAFFUD; CRAIK, DAVID J.. Cyclotides from Brazilian Palicourea sessilis and Their Effects on Human Lymphocytes. Journal of Natural Products, v. 84, n. 1, p. 81-90, JAN 22 2021. (19/04381-5, 17/17098-4, 13/07600-3)

FERNANDEZ-BOBEY, ANTONIO; FERREIRA PINTO, MERI EMILI; DE ALMEIDA, LARISSA COSTA; DE SOUZA, BIBIANA MONSON; DIAS, NATHALIA BAPTISTA; DE PAULA-SOUZA, JULIANA; CILLI, EDUARDO MAFFUD; LOPES, NORBERTO PEPORINE; COSTA-LOTUFO, LETICIA VERAS; PALMA, MARIO SERGIO; et al. Cytotoxic Cyclotides from Anchietea pyrifolia, a South American Plant Species. Journal of Natural Products, v. 85, n. 9, p. 8-pg., 2022-08-31. (14/50926-0, 19/04381-5, 20/02207-5, 14/25222-9, 13/07600-3, 19/26550-3, 17/17098-4, 16/16212-5)

RETZL, BERNHARD; HELLINGER, ROLAND; MURATSPAHIC, EDIN; PINTO, MERI E. F.; BOLZANI, VANDERLAN S.; GRUBER, CHRISTIAN W.. Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides. Journal of Natural Products, v. 83, n. 11, p. 3305-3314, NOV 25 2020. (19/04381-5)

QUEIROZ, SUZANA APARECIDA S.; PINTO, MERI EMILI F.; BOBEY, ANTONIO F.; RUSSO, HELENA M.; BATISTA, ANDREA N. L.; BATISTA, JR., JOAO M.; CODO, ANA C.; MEDEIROS, ALEXANDRA I.; BOLZANI, VANDERLAN S.. Diterpenoids with inhibitory activity of nitrite production from Croton floribundus. Journal of Ethnopharmacology, v. 249, MAR 1 2020. (19/04381-5, 13/07600-3, 14/25222-9, 17/19870-6, 17/18807-9, 14/50926-0, 17/17098-4)