Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation
| Autor: | Danubia Batista Martins, Carolina Colombelli Pacca, Marcia Perez dos Santos Cabrera, Bibiana Monson de Souza, Manoel Arcisio-Miranda, Annielle Mendes Brito da Silva, Mario Sergio Palma, Margarete Teresa Gottardo de Almeida |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Faceres Medical School, Universidade Federal de São Paulo (UNIFESP), Faculdade de Medicina de São José do Rio Preto |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Peptide–membrane interactions Staphylococcus aureus medicine.drug_class Clinical Biochemistry Antibiotics Endogeny Peptide Antineoplastic Agents medicine.disease_cause Arginine Biochemistry Hemolysis Aggregation Jelleine-I 03 medical and health sciences Mice Anti-Infective Agents medicine Animals Humans Melanoma Candida chemistry.chemical_classification 030102 biochemistry & molecular biology Chemistry Organic Chemistry Cell Membrane Tryptophan Zeta potential Antimicrobial Antimicrobial and anticancer peptides 030104 developmental biology Membrane Streptococcus pneumoniae Lytic cycle Toxicity Short-chain peptides Oligopeptides Antimicrobial Cationic Peptides |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1438-2199 |
| Popis: | Made available in DSpace on 2020-12-12T02:07:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Increasing resistance in antibiotic and chemotherapeutic treatments has been pushing studies of design and evaluation of bioactive peptides. Designing relies on different approaches from minimalist sequences and endogenous peptides modifications to computational libraries. Evaluation relies on microbiological tests. Aiming a deeper understanding, we chose the octapeptide Jelleine-I (JI) for its selective and low toxicity profile, designed small modifications combining the substitutions of Phe by Trp and Lys/His by Arg and tested the antimicrobial and anticancer activity on melanoma cells. Biophysical methods identified environment-dependent modulation of aggregation, but critical aggregation concentrations of JI and analogs in buffer show that peptides start membrane interactions as monomers. The presence of model membranes increases or reduces the partial aggregation of peptides. Compared to JI, analog JIF2WR shows the lowest tendency to aggregation on bacterial model membranes. JI and analogs are lytic to model membranes. Their composition-dependent performance indicates preference for the higher charged anionic bilayers in line with their superior performance toward Staphylococcus aureus and Streptococcus pneumoniae. JIF2WR presented the higher partitioning, higher lytic activity and lower aggregated contents. Despite these increased membranolytic activities, JIF2WR exhibited comparable antimicrobial activity in relation to JI at the expenses of some loss in selectivity. We found that the substitution Phe/Trp (JIF2W) tends to decrease antimicrobial but to increase anticancer activity and aggregation on model membranes and the toxicity toward human cells. However, the concomitant substitution Lys/His by Arg (JIF2WR) modulates some of these tendencies, increasing both the antimicrobial and the anticancer activity while decreasing the aggregation tendency. Departamento de Física Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265 Departamento de Química e Ciências Ambientais Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265 Faceres Medical School Laboratório de Neurobiologia Estrutural e Funcional (LaNEF) Departamento de Biofísica Universidade Federal de São Paulo R. Botucatu, 862, Edifício ECB, 7º andar Centro de Estudos de Insetos Sociais Universidade Estadual Paulista (Unesp), Câmpus Rio Claro, Av. 24-A, 1515 Departamento de Doenças Dermatológicas Infecciosas e Parasitárias Faculdade de Medicina de São José do Rio Preto Departamento de Física Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265 Departamento de Química e Ciências Ambientais Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265 Centro de Estudos de Insetos Sociais Universidade Estadual Paulista (Unesp), Câmpus Rio Claro, Av. 24-A, 1515 FAPESP: 2012/24259-0 FAPESP: 2014/08372-7 FAPESP: 2016/13368-4 FAPESP: 2016/16212-5 FAPESP: 2016/17951-6 |
| Databáze: | OpenAIRE |
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