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Antibacterial and anticancer activities of BP100 peptide and analogs containing Naphathalimide

Grant number: 18/15230-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2018
Effective date (End): September 30, 2021
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal researcher:Hernan Chaimovich Guralnik
Grantee:Gustavo Penteado Battesini Carretero
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/08166-5 - Interfacial chemistry: drugs, peptides and ezymes interactions with membrane models, AP.TEM


Antimicrobial peptides (AMPs) are a class of molecules existing in a large variety of organisms that work as a primary defense against pathogenic microorganisms. BP100 (KKLFKKILKYL-NH2) a short, highly cationic, synthetic AMP, is active against many bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires ±-helical conformation upon interaction with model membranes. The mechanism of action of BP100 depends on membrane surface charge and the amount of bound peptide. Despite the volume of information available, the mechanism of action of BP100, the selectivity of the biological effects of this peptide as well as its applications, are far from consensual. In this project we propose the use of fluorescent BP100 analogs containing naphthalimide and Di-naphthalimide synthesized by our collaborators. These BP100 derivatives were chosen because fluorescence properties of naphthalimides (especially spectral sensitivity to microenvironment changes) are well established and the activities against transformed cells are known. These results should contribute to better define the mechanism of action of BP100, evaluate its biological activity (antimicrobial, anticancer and toxicity) as well as to study the location of peptide in model membranes, prokaryotic and eukaryotic cells. Biophysical studies of the interaction of BP100 and analogues with model membranes of varied lipid composition will be performed by fluorescence, circular dichroism and dynamic light scattering. The peptide activity against liposomes will be investigated by permeabilization assay and microscopy of giant vesicles. The antimicrobial activity will be studied by determining the minimum inhibitory concentration of the peptides against different species of bacteria and by confocal fluorescence microscopy. The activity of the peptides against transformed eukaryotic cell lines will be accessed by cell viability and membrane permeability assays, and the localization of the peptides within those cells will be determined by confocal fluorescence microscopy. Finally, toxicity against human red blood cells will be determined.

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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)
CARRETERO, GUSTAVO PENTEADO BATTESINI; SARAIVA, GREICE KELLE VIEGAS; RODRIGUES, MAGALI APARECIDA; KIYOTA, SUMIKA; BEMQUERER, MARCELO PORTO; CHAIMOVICH, HERNAN; CUCCOVIA, IOLANDA MIDEA. Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity. BIOMOLECULES, v. 11, n. 4, . (18/15230-5, 14/50983-3, 13/08166-5, 15/10411-3)
DE SOUZA, VALDOMIRO V.; CARRETERO, GUSTAVO P. B.; VITALE, PHELIPE A. M.; TODESCHINI, IRIS; KOTANI, PALOMA O.; SARAIVA, V, GREICE K.; GUZZO, CRISTIANE R.; CHAIMOVICH, HERNAN; FLORENZANO, FABIO H.; CUCCOVIA, IOLANDA M.. Stimuli-responsive polymersomes of poly [2-(dimethylamino) ethyl methacrylate]-b-polystyrene. POLYMER BULLETIN, v. 79, n. 2, p. 785-805, . (13/08166-5, 18/15230-5)

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