Structure-Activity Relationship Studies on Novel Melittin Analogues

• Grant number: 25/06469-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: June 23, 2025
• End date: August 13, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Norival Alves Santos Filho
• Grantee: Leticia Rocha Casado
• Supervisor: Stephen Cochrane
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Queen's University Belfast, Northern Ireland
• Associated to the scholarship: 23/18398-2 - SYNTHESIS, CHARACTERIZATION AND STUDIES OF MECHANISMS of ACTION OF PEPTIDE ANALOGS MCF and MCFA, BP.IC

Abstract

Infectious diseases pose a significant challenge to global public health, accounting for hundreds of thousands of deaths annually. The improper use of antimicrobial agents has contributed to the rise of microbial resistance, leading to a reduction in the effectiveness of conventional treatments. In this context, antimicrobial peptides (AMPs), such as Melittin - composed of 26 amino acid residues and with a molecular mass of 2847,49 g/mol - emerge as promising alternatives due to their potent antimicrobial activity. However, the clinical application of these peptides is hindered by their high cytotoxicity. To overcome this limitation, the structural modification of peptides through amino acid substitutions has proven to be an effective strategy to enhance their biological properties, such as stability, selectivity, and antimicrobial activity. Substitutions of amino acids like lysine (Lys) with other cationic amino acids, for example, ornithine (Orn), diaminobutyric acid (Dab) or 2,4-diaminopimelic acid (Dap) that have shorter side chains, can reduce the lipophilicity of peptides, decreasing their cytotoxicity and conferring greater resistance to peptides. This study focuses on the synthesis of novel modified peptides with these substitutions, aiming to reduce their lipophilicity, improve their resistance to enzymatic degradation, and promote greater antimicrobial selectivity. The project involves evaluating the antimicrobial properties of these modified peptides against resistant strains, as well as their stability under biological conditions. It is expected that these modified peptides will provide significant advancements in the development of more effective and safer antimicrobial therapies, particularly in combating resistant infections. (AU)