Synthetic peptide derived from Scorpion venom displays minimal toxicity and anti-infective activity in an animal model

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dc.contributorLaboratório de Toxinologia Aplicadapt_BR
dc.contributor.authorOliveira, Cyntia Silvapt_BR
dc.contributor.authorTorres, Marcelo Der Torossianpt_BR
dc.contributor.authorPedron, Cibele Nicolaskipt_BR
dc.contributor.authorAndrade, Viviane Britopt_BR
dc.contributor.authorSilva Junior, Pedro Ismael dapt_BR
dc.contributor.authorSilva, Fernanda Diaspt_BR
dc.contributor.authorFuente-Nunez, Cesar de lapt_BR
dc.contributor.authorOliveira Jr, Vani Xavierpt_BR
dc.identifier.citationOliveira CS, Torres MDT, Pedron CN, Andrade VB, Silva Junior PI, Silva FD, et al. Synthetic peptide derived from Scorpion venom displays minimal toxicity and anti-infective activity in an animal model. ACS Infect Dis. 2021 Aug;9(7):2736–2745. doi:10.1021/acsinfecdis.1c00261.pt_BR
dc.description.abstractMultidrug-resistant bacteria represent a global health problem increasingly leading to infections that are untreatable with our existing antibiotic arsenal. Therefore, it is critical to identify novel effective antimicrobials. Venoms represent an underexplored source of potential antibiotic molecules. Here, we engineered a peptide (IsCT1-NH2) derived from the venom of the scorpion Opisthacanthus madagascariensis, whose application as an antimicrobial had been traditionally hindered by its high toxicity. Through peptide design and the knowledge obtained in preliminary studies with single and double-substituted analogs, we engineered IsCT1 derivatives with multiple amino acid substitutions to assess the impact of net charge on antimicrobial activity and toxicity. We demonstrate that increased net charge (from +3 to +6) significantly reduced toxicity toward human erythrocytes. Our lead synthetic peptide, [A]1[K]3[F]5[K]8-IsCT1-NH2 (net charge of +4), exhibited increased antimicrobial activity against Gram-negative and Gram-positive bacteria in vitro and enhanced anti-infective activity in a mouse model. Mechanism of action studies revealed that the increased antimicrobial activity of our lead molecule was due, at least in part, to its enhanced ability to permeabilize the outer membrane and depolarize the cytoplasmic membrane. In summary, we describe a simple method based on net charge tuning to turn highly toxic venom-derived peptides into viable therapeutics.pt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(UFABC) Universidade Federal do ABCpt_BR
dc.description.sponsorshipUniversity of Pennsylvaniapt_BR
dc.description.sponsorship(NIH) National Institutes of Healthpt_BR
dc.description.sponsorship(DTRA) Defense Threat Reduction Agencypt_BR
dc.description.sponsorship(IDOM) Institute for Diabetes, Obesity, and Metabolismpt_BR
dc.relation.ispartofACS Infectious Diseasespt_BR
dc.rightsRestricted accesspt_BR
dc.titleSynthetic peptide derived from Scorpion venom displays minimal toxicity and anti-infective activity in an animal modelpt_BR
dc.contributor.external(UNIFESP) Universidade Federal de São Paulopt_BR
dc.contributor.externalUniversity of Pennsylvaniapt_BR
dc.contributor.external(UFABC) Universidade Federal do ABCpt_BR
dc.subject.keywordantimicrobial peptidespt_BR
dc.subject.keywordpeptide therapeuticspt_BR
dc.subject.keywordESKAPE pathogenspt_BR
dc.subject.keywordstructure−activity relationshipspt_BR
dc.subject.keywordscorpion venompt_BR
dc.relation.ispartofabbreviatedACS Infect Dispt_BR
dc.identifier.citationabntv. 9, n. 7, p. 2736–2745, ago. 2021pt_BR
dc.identifier.citationvancouver2021 Aug;9(7):2736–2745pt_BR
dc.contributor.butantanSilva Junior, Pedro Ismael da|:Pesquisador|:Laboratório de Toxinologia Aplicadapt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦001pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2017/03046-2pt_BR
dc.sponsorship.butantan(UFABC) Universidade Federal do ABC¦¦pt_BR
dc.sponsorship.butantanUniversity of Pennsylvania¦¦pt_BR
dc.sponsorship.butantanNational Institutes of Health (NIH)¦¦R35GM138201pt_BR
dc.sponsorship.butantanDefense Threat Reduction Agency (DTRA)¦¦DTRA11810041pt_BR
dc.sponsorship.butantanDefense Threat Reduction Agency (DTRA)¦¦HDTRA1-21-1-0014pt_BR
dc.sponsorship.butantan(IDOM) Institute for Diabetes, Obesity, and Metabolism¦¦pt_BR
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