Adepamycin: design, synthesis and biological properties of a new peptide with antimicrobial properties
dc.contributor.author | Almeida, Luis Henrique de Oliveira | |
dc.contributor.author | Oliveira, Caio Fernando Ramalh de | |
dc.contributor.author | Rodrigues, Mayara de Souza | |
dc.contributor.author | Neto, Simone Maria | |
dc.contributor.author | Boleti, Ana Paula de Araujo | |
dc.contributor.author | Taveira, Gabriel Bonan | |
dc.contributor.author | Mello, Erica de Oliveira | |
dc.contributor.author | Gomes, Valdirene Moreira | |
dc.contributor.author | Santos, Edson Luca dos | |
dc.contributor.author | Crusca Jr, Edson [UNESP] | |
dc.contributor.author | Franco, Octavio Luiz | |
dc.contributor.author | Cardoso, Marlon Henrique e Silva | |
dc.contributor.author | Macedo, Maria Ligia Rodrigues | |
dc.contributor.institution | Universidade Federal de Mato Grosso do Sul (UFMS) | |
dc.contributor.institution | Fundacao Univ Fed Grande Dourados | |
dc.contributor.institution | Univ Catolica Brasilia | |
dc.contributor.institution | Univ Catolica Dom Bosco | |
dc.contributor.institution | Univ Estadual Norte Fluminense | |
dc.contributor.institution | Universidade Estadual Paulista (Unesp) | |
dc.date.accessioned | 2021-06-25T11:21:00Z | |
dc.date.available | 2021-06-25T11:21:00Z | |
dc.date.issued | 2020-09-30 | |
dc.description.abstract | Antimicrobial peptides (AMP) are molecules with a broad spectrum of activities that have been identified in most living organisms. In addition, synthetic AMPs designed from natural polypeptides have been largely investigated. Here, we designed a novel AMP using the amino acid sequence of a plant trypsin inhibitor from Adenanthera pavonina seeds (ApTI) as a template. The 176 amino acid residues ApTI sequence was cleaved in silico using the Collection of Antimicrobial Peptides (CAMPR3), through the sliding-window method. Further improvements in AMP structure were carried out, resulting in adepamycin, an AMP designed from ApTI. Adepamycin showed antimicrobial activity from 0.9 to 3.6 mu M against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Moreover, this peptide also displayed activity against Candida albicans and Candida tropicalis. No toxic effects were observed on healthy human cells. Studies on the mechanism of action of adepamycin were carried out using an E. coli and C. tropicalis. Adepamycin triggers membrane disturbances, leading to intracellular nucleic acids release in E. coli. For C. tropicalis, an initial interference with the plasma membrane integrity is followed by the formation of intracellular reactive oxygen species (ROS), leading to apoptosis. Structurally, adepamycin was submitted to circular dichroism spectroscopy, molecular modeling and molecular dynamics simulations, revealing an environment dependent alpha-helical structure in the presence of 2,2,2- trifluoroethanol (TFE) and in contact with mimetic vesicles/membranes. Therefore, adepamycin represents a novel lytic AMP with dual antibacterial and antifungal properties. | en |
dc.description.affiliation | Univ Fed Mato Grosso do Sul, Lab Purificacao Prot & Suas Funcoes Biol, BR-79070900 Campo Grande, MS, Brazil | |
dc.description.affiliation | Fundacao Univ Fed Grande Dourados, BR-79804970 Dourados, MS, Brazil | |
dc.description.affiliation | Univ Catolica Brasilia, Ctr Anal Prote & Bioquim, BR-70790160 Brasilia, DF, Brazil | |
dc.description.affiliation | Univ Catolica Dom Bosco, S Inova Biotech, BR-79117010 Campo Grande, MS, Brazil | |
dc.description.affiliation | Univ Estadual Norte Fluminense, Lab Bioquim & Fisiol Microrganismos, BR-28013602 Campo Dos Goytacazes, RJ, Brazil | |
dc.description.affiliation | Univ Estadual Paulista, BR-14800060 Araraquara, SP, Brazil | |
dc.description.affiliationUnesp | Univ Estadual Paulista, BR-14800060 Araraquara, SP, Brazil | |
dc.description.sponsorship | Fundacao Universidade Federal de Mato Grosso do Sul - UFMS/MEC - Brazil | |
dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | |
dc.description.sponsorship | Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul - Brasil (FUNDECT) | |
dc.description.sponsorship | Fundacao de Apoio a Pesquisa do Distrito Federal - Brasil (FAP-DF) | |
dc.description.sponsorship | Financiadora de Estudos e Projetos (FINEP) | |
dc.description.sponsorshipId | CAPES: 001 | |
dc.description.sponsorshipId | CNPq: 430694/2016-4 | |
dc.description.sponsorshipId | CNPq: 305679/2016-3 | |
dc.description.sponsorshipId | CNPq: 426912/2018-7 | |
dc.description.sponsorshipId | Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul - Brasil (FUNDECT): 16/2014 | |
dc.description.sponsorshipId | Fundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul - Brasil (FUNDECT): 047/2018 | |
dc.format.extent | 12 | |
dc.identifier | http://dx.doi.org/10.1016/j.abb.2020.108487 | |
dc.identifier.citation | Archives Of Biochemistry And Biophysics. New York: Elsevier Science Inc, v. 691, 12 p., 2020. | |
dc.identifier.doi | 10.1016/j.abb.2020.108487 | |
dc.identifier.issn | 0003-9861 | |
dc.identifier.uri | http://hdl.handle.net/11449/208804 | |
dc.identifier.wos | WOS:000568860500004 | |
dc.language.iso | eng | |
dc.publisher | Elsevier B.V. | |
dc.relation.ispartof | Archives Of Biochemistry And Biophysics | |
dc.source | Web of Science | |
dc.subject | Rational design | |
dc.subject | Antimicrobial peptides | |
dc.subject | Pathogenic bacteria | |
dc.subject | Pathogenic yeast | |
dc.title | Adepamycin: design, synthesis and biological properties of a new peptide with antimicrobial properties | en |
dc.type | Artigo | |
dcterms.license | http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy | |
dcterms.rightsHolder | Elsevier B.V. |