Evaluation of protease inhibitory properties and biological activities from Allexis cauliflora's cyclotides for application in animal nutrition

• Grant number: 22/02808-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2022
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Eduardo Festozo Vicente
• Grantee: Ndogo Eteme Olivier
• Host Institution: Faculdade de Ciências e Engenharia. Universidade Estadual Paulista (UNESP). Campus de Tupã. Tupã , SP, Brazil
• Associated research grant: 21/06706-9 - Antimicrobial peptides: expanding the horizons for animal production performance optimization, AP.JP2

Abstract

Peptides are considered less toxic than small molecules. However, one drawback is their lack of stability, particularly in the gastrointestinal tract, due to natural degradation by proteases and acidic environment. To overcome this obstacle, we will use disulphide-stabilized peptides derived from the repertoire of Nature. For example, Violaceae family plants are a rich source of cyclic cystine-knot peptides called cyclotides and sunflowers produce cyclic sunflower trypsin inhibitors. During the project, we will extract novel cyclotides from Allexis cauliflora, determine their sequence, characterize them and measure their ability to inhibit proteases and determine the biological activities. To improve their properties, we will use grafting strategies and synthesize them by solid-phase peptide synthesis. In addition, we will use and develop bioinformatics methods to explore their distribution, evolution, and biological activities improvements. Finally, the best molecules will be selected for animal nutrition application. This postdoctoral project will be of great value in the candidate's academic and professional training and will also contribute to Prof. Dr. Eduardo Festozo Vicente research group bringing the expertise of new several biophysical techniques, bioinformatics to study cyclotides applied to a human disease. In addition, the experience acquired by the candidate in his internship abroad will add to the existing efforts in the supervisor's group to establish the solid phase peptide synthesis nucleation at SSE/Tupã. Thus, with the realization of the new cyclotide syntheses proposed in this project and using the mass spectroscopy techniques, which will be used more intensely, we believe that this partnership will have fundamental importance both in the candidate's academic training and in the consolidation of the PeSEAp research group and applications in structural biology and animal science.