Development and study of new peptide compounds with potential to act as antimicrobial, cell-penetrating and/or metal-chelating agents

• Grant number: 22/01825-2
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2022
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Maria Teresa Machini
• Grantee: Maria Teresa Machini
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Breno Pannia Esposito ; Rebeca Garcia Moura ; Roberto Kopke Salinas

Abstract

Progressive increase of animal infections caused by pathogenic microorganisms (1), microbial persistence & resistance to the antibiotics (2), degenerative diseases associated with essential metals (3), animal health & feed endless demand for more specific compounds, more agile efficient methods (4) are topics of broad interest to the global scientific community, health professionals and general human population. Thus, basic research focused on new antibacterial, antifungal, surfactant, cell-penetrating and essential metal-chelating agents is urgent and valued. The goal of our research project is to develop and study new peptides and peptide conjugates that are active on pathogenic microorganisms, penetrate cells and/or bind essential divalent metals. Our molecular targets are the candidacidal Shepherin I and its truncated analogues, peptide inhibitors of the E. coli toxin MazF and conjugates encompassing short amphipathic antimicrobial peptides, cell penetrating peptides and/or antibiotics. Our objectives are: 1. To establish synthetic and analytical routes to obtain and properly characterize our targets; 2. To examine their structure-function relationships; 3. To collect data on the targets´structures in membrane-mimetic systems; 4. To understand their modes of action; 5. To develop improved analogues of our targets; 6. To verify potential applications of such macromolecules, which might include: (i) attempts to disinfect medical and dental devices and/or food, (ii) attempts to treat animal microbial infections, (iii) analysis of effects on copper-dependent biological events (such as beta-amyloid plaque formation and angiogenesis) using appropriate cellular models, (iv) detection and quantification of divalent metal ions in liquid samples (v) drug delivery on cell cultures. Given the interdisciplinary nature of the research, we will collaborate with researchers with complementary backgrounds and expertises. (AU)

Scientific publications

(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)

LACERDA, C. D.; JULIANO, M. A.; LIRIA, C. W.; MACHINI, M. T.; PARK, P.; MATSUBARA, D. K.; BARZOTTO, D. R.; LIMA, F. S.; CHAIMOVICH, H.; CUCCOVIA, I. M.. Position matters in ester thiolysis by cysteine-containing peptides in micelles and vesicles. RESULTS IN CHEMISTRY, v. 6, p. 10-pg., 2023-12-01. (19/03023-8, 14/50983-3, 15/10411-3, 22/01825-2, 13/08166-5)