Adepamycin: design, synthesis and biological properties of a new peptide with antimicrobial properties

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dc.contributor.authorAlmeida, Luis Henrique de Oliveira
dc.contributor.authorOliveira, Caio Fernando Ramalh de
dc.contributor.authorRodrigues, Mayara de Souza
dc.contributor.authorNeto, Simone Maria
dc.contributor.authorBoleti, Ana Paula de Araujo
dc.contributor.authorTaveira, Gabriel Bonan
dc.contributor.authorMello, Erica de Oliveira
dc.contributor.authorGomes, Valdirene Moreira
dc.contributor.authorSantos, Edson Luca dos
dc.contributor.authorCrusca Jr, Edson [UNESP]
dc.contributor.authorFranco, Octavio Luiz
dc.contributor.authorCardoso, Marlon Henrique e Silva
dc.contributor.authorMacedo, Maria Ligia Rodrigues
dc.contributor.institutionUniversidade Federal de Mato Grosso do Sul (UFMS)
dc.contributor.institutionFundacao Univ Fed Grande Dourados
dc.contributor.institutionUniv Catolica Brasilia
dc.contributor.institutionUniv Catolica Dom Bosco
dc.contributor.institutionUniv Estadual Norte Fluminense
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2021-06-25T11:21:00Z
dc.date.available2021-06-25T11:21:00Z
dc.date.issued2020-09-30
dc.description.abstractAntimicrobial 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.affiliationUniv Fed Mato Grosso do Sul, Lab Purificacao Prot & Suas Funcoes Biol, BR-79070900 Campo Grande, MS, Brazil
dc.description.affiliationFundacao Univ Fed Grande Dourados, BR-79804970 Dourados, MS, Brazil
dc.description.affiliationUniv Catolica Brasilia, Ctr Anal Prote & Bioquim, BR-70790160 Brasilia, DF, Brazil
dc.description.affiliationUniv Catolica Dom Bosco, S Inova Biotech, BR-79117010 Campo Grande, MS, Brazil
dc.description.affiliationUniv Estadual Norte Fluminense, Lab Bioquim & Fisiol Microrganismos, BR-28013602 Campo Dos Goytacazes, RJ, Brazil
dc.description.affiliationUniv Estadual Paulista, BR-14800060 Araraquara, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, BR-14800060 Araraquara, SP, Brazil
dc.description.sponsorshipFundacao Universidade Federal de Mato Grosso do Sul - UFMS/MEC - Brazil
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul - Brasil (FUNDECT)
dc.description.sponsorshipFundacao de Apoio a Pesquisa do Distrito Federal - Brasil (FAP-DF)
dc.description.sponsorshipFinanciadora de Estudos e Projetos (FINEP)
dc.description.sponsorshipIdCAPES: 001
dc.description.sponsorshipIdCNPq: 430694/2016-4
dc.description.sponsorshipIdCNPq: 305679/2016-3
dc.description.sponsorshipIdCNPq: 426912/2018-7
dc.description.sponsorshipIdFundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul - Brasil (FUNDECT): 16/2014
dc.description.sponsorshipIdFundacao de Apoio ao Desenvolvimento do Ensino, Ciencia e Tecnologia do Estado de Mato Grosso do Sul - Brasil (FUNDECT): 047/2018
dc.format.extent12
dc.identifierhttp://dx.doi.org/10.1016/j.abb.2020.108487
dc.identifier.citationArchives Of Biochemistry And Biophysics. New York: Elsevier Science Inc, v. 691, 12 p., 2020.
dc.identifier.doi10.1016/j.abb.2020.108487
dc.identifier.issn0003-9861
dc.identifier.urihttp://hdl.handle.net/11449/208804
dc.identifier.wosWOS:000568860500004
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofArchives Of Biochemistry And Biophysics
dc.sourceWeb of Science
dc.subjectRational design
dc.subjectAntimicrobial peptides
dc.subjectPathogenic bacteria
dc.subjectPathogenic yeast
dc.titleAdepamycin: design, synthesis and biological properties of a new peptide with antimicrobial propertiesen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.

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