Light emitting arginine derivatives as tags for antimicrobial peptides

• Grant number: 19/15871-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): November 01, 2019
• Effective date (End): October 31, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Fernando Heering Bartoloni
• Grantee: Andréia Boaro
• Supervisor: Cesar de La Fuente-Nunez
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Research place: University of Pennsylvania, United States
• Associated to the scholarship: 16/10585-4 - Mechanistic aspects regarding the induced decomposition of hydroperoxides and silylperoxides derived from lophine, BP.DR

Abstract

The increase in multidrug-resistant pathogens has led to the search for new antibiotics. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics due to their broad-spectrum activity, their potency at low concentrations, and their multifunctional mode of action that decreases the likelihood of resistance development. This research project aims to search for new candidate fluorescent and chemiluminescent taggers to enable tagging of AMPs effectively and without interfering in their structural and physicochemical features. This will help with insights on mechanisms of action and bioavailability of these molecules in vitro (growth inhibition and antibiofilm assays) and in animal models. Such tags are synthetic arginine derivatives obtained by one-pot multicomponent condensation, containing a fluorescent imidazole core that can be photoconverted to linear peroxides. The deprotection of these peroxides, under adequate conditions, conveniently generates chemiluminescence light, useful for substrates detection and quantification. Through this project, the student will learn new techniques relevant for peptide design and engineering (e.g., structure-activity relationship studies), massively parallel peptide synthesis, functional characterization of peptide activity (i.e., antimicrobial and antibiofilm assays), and will acquire skills to perform experiments using animal models, and whole-animal imaging techniques. Also, the student will be able to apply her expertise on multicomponent preparations and organic peroxides synthesis on a practical and challenging problem thus significantly expanding her research skills.

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)

BOARO, ANDREIA; REIS, ROBERTA ALBINO; SILVA, CAROLINA SANTANA; MELO, DIEGO ULYSSES; GONCALVES COSTA PINTO, ALEXANDER GARRETA; BARTOLONI, FERNANDO HEERING. Evidence for the Formation of 1,2-Dioxetane as a High-Energy Intermediate and Possible Chemiexcitation Pathways in the Chemiluminescence of Lophine Peroxides. Journal of Organic Chemistry, v. 86, n. 9, p. 6633-6647, MAY 7 2021. (12/13807-7, 19/15871-3, 16/10585-4)

BOARO, ANDREIA; AGEITOS, LUCIA; TORRES, MARCELO; BARTOLONI, FERNANDO HEERING; DE LA FUENTE-NUNEZ, CESAR. Light-Emitting Probes for Labeling Peptides. CELL REPORTS PHYSICAL SCIENCE, v. 1, n. 12, DEC 23 2020. (19/15871-3, 16/10585-4)