C-terminal truncated sequences of Ctx(Ile21)-Ha antimicrobial peptide: decreasing molecular mass to increase biological activity

• Grant number: 22/01544-3
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2022
• Effective date (End): December 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal researcher: Eduardo Festozo Vicente
• Grantee: Matheus Marchetti Melo
• Home 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

In order to exert their varied biological activity against different microorganisms, antimicrobial peptides need to present different physicochemical characteristics such as helicity, amphipathicity, hydrophobicity and cationicity. These properties, when integrated and modulated, can promote an increase or a decrease in its biological activity. In addition, it is known that the N-terminal region of antimicrobial peptides is fundamental for the initial interaction with the cell membrane. In addition, small peptides provide facilities and quickness in their synthesis and, at the same time, their production cost can be drastically reduced. In this sense, this project aims to truncate the primary sequence of the antimicrobial peptide Ctx(Ile21)-Ha from its C-terminal end, which will decrease the molecular weight of the produced analogs, in an attempt to optimize their biological activities. For this, six Ctx(Ile21)-Ha peptide analogues will be strategically synthesized, where the smallest analogue will have only eleven residues, starting from the N-terminal end, respecting at least three alpha-helix turns, considering 3.6 residues per helice turn. In this way, after their proper synthesis, purification, and characterization, the secondary structures of the analogs will be analyzed, via circular dichroism, using membrane mimetics. Those peptides that maintain the alpha-helix structures in membrane mimetics will be evaluated for their biological activities against microorganisms of interest to human and animal public health (Salmonella sp., Escherichia coli, Staphiloccocus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, etc.). It is expected, with this project, that analogs of the antimicrobial peptide Ctx(Ile21)-Ha will be developed with a lower molecular weight and with more potent antimicrobial activities against the pathogens of interest.(AU)