Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells

• Grant number: 12/24259-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2013
• End date: April 30, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Marcia Perez dos Santos Cabrera
• Grantee: Marcia Perez dos Santos Cabrera
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated research grant(s): 16/50187-8 - Antimicrobial, anticancer peptides and peptide/chitosan conjugates characterization by AFM (Atomic force microscopy), AP.R SPRINT
• Associated scholarship(s): 15/07548-7 - New route for synthesis of conjugates peptide-chitosan: the effects of the peptide's hydrophobicity evaluated on model membranes interaction via zeta potential, BP.IC; 14/08372-7 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells, BP.JP

Abstract

One of the main advantages in the use of antimicrobial peptides in antibiotic therapy is the reduced chance of resistance development, since these peptides target the cell membrane phospholipid matrix. Mechanisms of the selective action found in some bioactive peptides are investigated as a means to orient structural optimizations that can enhance the therapeutic action and at the same time minimizing toxic or undesirable side effects. Moreover studies carried out in model membranes have evidenced that features of the lipid composition of bilayers are important for selectivity and to our understanding of facts derived from this interaction. Chitosans and some of its cationic derivatives similarly modify the characteristics of lipid bilayers through mechanisms much less known and studied. This project intends to synthesize a series of new molecules, which are conjugates of antimicrobial and/or tumoricidal peptides and modified chitosans, looking forward to increased efficiency in the biological activity and to lower toxicity. Since peptides, chitosans and other anphiphilic molecules exert activity on the phospholipid matrix through mechanisms, which are not well understood, studies of the interaction of these conjugated molecules with the lipid bilayer will be carried out to evaluate the relationship composition/structure/activity on model cell membranes. Additionally cytotoxicity and biological activity experiments in vitro will be performed to help selecting the best conjugated molecules for future evaluation in vivo. (AU)

Scientific publications

(19)

(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)

LEITE, NATALIA B.; MARTINS, DANUBIA B.; FAZANI, VINICIUS E.; VIEIRA, MAIRA R.; DOS SANTOS CABRERA, MARCIA P.. Cholesterol modulates curcumin partitioning and membrane effects. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1860, n. 11, p. 2320-2328, NOV 2018. (14/06713-1, 14/08372-7, 14/11877-3, 12/24259-0)

LAURENTI, JULIANA BERGAMASCO; ZAZERI, GABRIEL; RIBEIRO POVINELLI, ANA PAULA; DE GODOY, MOACIR FERNANDES; BRAILE, DOMINGO MARCOLINO; FLORES DA ROCHA, TANIA R.; D' AMICO, ELBIO ANTONIO; NERY, JOSE GERALDO. Enhanced pro-coagulant hemostatic agents based on nanometric zeolites. Microporous and Mesoporous Materials, v. 239, p. 263-271, FEB 2017. (13/16754-4, 12/24259-0)

SILVA, K. S.; FONSECA, T. M. R.; AMADO, L. R.; MAURO, M. A.. Physicochemical and microstructural properties of whey protein isolate-based films with addition of pectin. FOOD PACKAGING AND SHELF LIFE, v. 16, p. 122-128, JUN 2018. (17/02808-6, 12/24259-0)

MARTINS, DANUBIA BATISTA; FADEL, VALMIR; OLIVEIRA, FILIPA D.; GASPAR, DIANA; ALVARES, DAYANE S.; CASTANHO, MIGUEL A. R. B.; CABRERA, MARCIA PEREZ DOS SANTOS. Protonectin peptides target lipids, act at the interface and selectively kill metastatic breast cancer cells while preserving morphological integrity. Journal of Colloid and Interface Science, v. 601, p. 517-530, NOV 2021. (15/25620-7, 14/08372-7, 12/24259-0)

MEDEIROS, DJALMA; SILVA-GONCALVES, LAIZ DA COSTA; BRITO DA SILVA, ANNIELLE MENDES; DOS SANTOS CABRERA, MARCIA PEREZ; ARCISIO-MIRANDA, MANOEL. Membrane-mediated action of the endocannabinoid anandamide on membrane proteins: implications for understanding the receptor-independent mechanism. SCIENTIFIC REPORTS, v. 7, JAN 27 2017. (12/02065-0, 12/24259-0, 14/08372-7)

MARTINS, DANUBIA BATISTA; VIEIRA, MAIRA RAMOS; FADEL, VALMIR; CAMARGO SANTANA, VIVIANE APARECIDA; RODRIGUES GUERR, MIRIAN ELISA; LIMA, MARTA LOPES; TEMPONE, ANDRE G.; DOS SANTOS CABRERA, MARCIA PEREZ. Membrane targeting peptides toward antileishmanial activity: Design, structural determination and mechanism of interaction. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 11, A, p. 2861-2871, NOV 2017. (15/17331-5, 12/24259-0, 14/11877-3, 14/08372-7, 13/50228-8)

RANGEL, MARISA; DOS SANTOS CASTRO, FABIOLA FERNANDES; MOTA-LIMA, LILIAN DAIENE; CLISSA, PATRICIA BIANCA; MARTINS, DANUBIA BATISTA; DOS SANTOS CABRERA, MARCIA PEREZ; MORTARI, MARCIA RENATA. Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction. PLoS One, v. 12, n. 6, JUN 1 2017. (12/24259-0, 14/08372-7, 08/00173-4)

DOS SANTOS CABRERA, MARCIA PEREZ; BALDISSERA, GISELE; SILVA-GONCALVES, LAIZ DA COSTA; DE SOUZA, BIBIANA MONSON; RISKE, KARIN A.; PALMA, MARIO SERGIO; RUGGIERO, JOSE ROBERTO; ARCISIO-MIRANDA, MANOEL. Combining Experimental Evidence and Molecular Dynamic Simulations To Understand the Mechanism of Action of the Antimicrobial Octapeptide Jelleine-I. BIOCHEMISTRY, v. 53, n. 29, p. 4857-4868, JUL 29 2014. (06/57122-7, 10/11823-0, 10/52077-9, 12/24259-0, 11/51684-1)

COSTA PETRIN, THAIS H.; FADEL, VALMIR; MARTINS, DANUBIA B.; DIAS, SUSANA A.; CRUZ, ANA; SERGIO, LUCIANA MARCIANO; ARCISIO-MIRANDA, MANOEL; CASTANHO, MIGUEL A. R. B.; DOS SANTOS CABRERA, MARCIA P.. Synthesis and Characterization of Peptide-Chitosan Conjugates (PepChis) with Lipid Bilayer Affinity and Antibacterial Activity. Biomacromolecules, v. 20, n. 7, p. 2743-2753, JUL 2019. (14/08372-7, 16/13368-4, 15/07548-7, 12/02065-0, 12/24259-0)

MARTINS, DANUBIA BATISTA; NASARIO, FABIO DOMINGUES; SILVA-GONCALVES, LAIZ COSTA; DE OLIVEIRA TIERA, VERA APARECIDA; ARCISIO-MIRANDA, MANOEL; TIERA, MARCIO JOSE; DOS SANTOS CABRERA, MARCIA PEREZ. Chitosan derivatives targeting lipid bilayers: Synthesis, biological activity and interaction with model membranes. Carbohydrate Polymers, v. 181, p. 1213-1223, FEB 1 2018. (12/02065-0, 09/11707-2, 10/11823-0, 12/24259-0, 12/03619-9, 14/08372-7)

RODRIGUES GUERRA, MIRIAN ELISA; FADEL, VALMIR; MALTAROLLO, VINICIUS GONCALVES; BALDISSERA, GISELE; HONORIO, KATHIA MARIA; RUGGIERO, JOSE ROBERTO; DOS SANTOS CABRERA, MARCIA PEREZ. MD simulations and multivariate studies for modeling the antileishmanial activity of peptides. CHEMICAL BIOLOGY & DRUG DESIGN, v. 90, n. 4, p. 501-510, OCT 2017. (06/57122-7, 12/24259-0, 14/08372-7)

LEITE, NATALIA BUENO; MARTINS, DANUBIA BATISTA; ALVARES, DAYANE S.; DOS SANTOS CABRERA, MARCIA PEREZ. Quercetin induces lipid domain-dependent permeability. Chemistry and Physics of Lipids, v. 242, p. 11-pg., 2022-01-01. (14/11877-3, 14/06713-1, 12/24259-0, 14/08372-7)

DE OLIVEIRA, MARIA MARIANA GARCIA; DE SOUZA SILVA, KEILA; MAURO, MARIA APARECIDA. Evaluation of Interactions Between Carboxymethylcellulose and Soy Protein Isolate and their Effects on the Preparation and Characterization of Composite Edible Films. FOOD BIOPHYSICS, v. 16, n. 2, JAN 2021. (17/08544-0, 17/02808-6, 12/24259-0)

MARTINS, DANUBIA BATISTA; VIEIRA, MAIRA RAMOS; FADEL, VALMIR; CAMARGO SANTANA, VIVIANE APARECIDA; RODRIGUES GUERR, MIRIAN ELISA; LIMA, MARTA LOPES; TEMPONE, ANDRE G.; DOS SANTOS CABRERA, MARCIA PEREZ. Membrane targeting peptides toward antileishmanial activity: Design, structural determination and mechanism of interaction. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 11, p. 11-pg., 2017-11-01. (13/50228-8, 14/11877-3, 12/24259-0, 14/08372-7, 15/17331-5)

MARTINS, DANUBIA BATISTA; PACCA, CAROLINA COLOMBELLI; DA SILVA, ANNIELLE MENDES BRITO; DE SOUZA, BIBIANA MONSON; DE ALMEIDA, MARGARETE TERESA GOTTARDO; PALMA, MARIO SERGIO; ARCISIO-MIRANDA, MANOEL; DOS SANTOS CABRERA, MARCIA PEREZ. Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation. Amino Acids, v. 52, n. 5, MAY 2020. (16/16212-5, 16/13368-4, 16/17951-6, 14/08372-7, 12/24259-0)

MARTINS, GRAZIELI OLINDA; PETRONIO, MAICON SEGALLA; FURUYAMA LIMA, ALINE MARGARETE; MARTINEZ JUNIOR, ANDRE MIGUEL; DE OLIVEIRA TIERA, VERA APARECIDA; CALMON, MARILIA DE FREITAS; LEITE VILAMAIOR, PATRICIA SIMONE; HAN, SANG WON; TIERA, MARCIO JOSE. Amphipathic chitosans improve the physicochemical properties of siRNA-chitosan nanoparticles at physiological conditions. Carbohydrate Polymers, v. 216, p. 332-342, JUL 15 2019. (17/10331-5, 12/24259-0, 15/05148-1, 15/20206-8)

DE VASCONCELLOS, ADRIANO; MILLER, ALEX HENRIQUE; ARANDA, DONATO A. G.; NERY, JOSE GERALDO. Biocatalysts based on nanozeolite-enzyme complexes: Effects of alkoxysilane surface functionalization and biofuel production using microalgae lipids feedstock. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 165, p. 150-157, MAY 1 2018. (12/24259-0, 11/10092-4, 11/51851-5, 16/24303-0)

MUNARI BENETTI, JOAO VITOR; DO PRADO SILVA, JESSICA THAIS; NICOLETTI, VANIA REGINA. SPI microgels applied to Pickering stabilization of O/W emulsions by ultrasound and high-pressure homogenization: rheology and spray drying. Food Research International, v. 122, p. 383-391, AUG 2019. (16/22727-8, 12/24259-0)

CHAUX-GUTIERREZ, ANA MARIA; PEREZ-MONTERROZA, EZEQUIEL JOSE; MAURO, MARIA APARECIDA. Rheological and structural characterization of gels from albumin and low methoxyl amidated pectin mixtures. FOOD HYDROCOLLOIDS, v. 92, p. 60-68, JUL 2019. (17/02808-6, 12/24259-0)