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Structural determinants conferring unusual long life in human serum to rattlesnake‐derived antimicrobial peptide Ctn(15‐34)

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dc.contributor.authorPérez‐Peinado, Clara
dc.contributor.authorDias, Susana
dc.contributor.authorMendonça, Diogo A.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorVeiga, Ana Salomé
dc.contributor.authorAndreu, David
dc.date.accessioned2021-10-22T14:35:40Z
dc.date.available2021-10-22T14:35:40Z
dc.date.issued2019
dc.description© 2019 European Peptide Society and John Wiley & Sons, Ltd.pt_PT
dc.description.abstractCtn[15-34], a downsized version of the snake venom cathelicidin-like peptide crotalicidin (Ctn), shows an unusually high lifespan (t1/2 , approximately 12 h) in human serum, which significantly adds to its promise as an antimicrobial and antitumor agent. Herein we investigate the role of Ctn[15-34] structure on serum survival. Using a set of analogs, we show that C-terminal amidation, as well as the specific layout of the Ctn[15-34] sequence-a helical N-terminal domain followed by a hydrophobic domain-is crucial for slow degradation, and any change in their arrangement results in significantly lower t1/2 . Aside from the privileged primary structure, features such as self-aggregation can be ruled out as causes for the long serum life. Instead, studies in other protease-rich fluids suggest a key role for certain human serum components. Finally, we demonstrate that Ctn[15-34] is able to induce bacterial death even after 12-hour pre-incubation in serum, in agreement with the proteolytic data. Altogether, the results shed light on the uncommon stability of Ctn[15-34] in human serum and confirm its potential as an anti-infective lead.pt_PT
dc.description.sponsorshipThis work was supported by grants SAF2011-24899, AGL2014-52395-C2 and AGL2017-84097-C2-2-R from the Spanish Ministry of Economy and Competitiveness (MINECO), by Fundação para a Ciência e a Tecnologia (FCT, Portugal) grant PTDC/QEQ-MED/4412/2014, and by the EU Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) program grant 644167, 2015-2019. C.P.-P. acknowledges the MINECO “María de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0370) for a predoctoral fellowship. S.A.D., D.A.M., and A.S.V. also acknowledge FCT for fellowships PD/BD/114425/2016, PD/BD/136752/2018, and funding under the Investigator Program IF/00803/2012.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Pept Sci. 2019 Aug;25(8):e3195pt_PT
dc.identifier.doi10.1002/psc.3195pt_PT
dc.identifier.eissn1099-1387
dc.identifier.issn1075-2617
dc.identifier.urihttp://hdl.handle.net/10451/49982
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationIF/00803/2012pt_PT
dc.relationTowards the development of innovative highly effective dual action anti-HIV peptides
dc.relationInnovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training , and communication.
dc.relationTowards the development of antimicrobial peptides active against bacterial biofilms
dc.relationTargeting brain-resident viruses across the blood-brain barrier using peptide drugs.
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/10991387pt_PT
dc.titleStructural determinants conferring unusual long life in human serum to rattlesnake‐derived antimicrobial peptide Ctn(15‐34)pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTowards the development of innovative highly effective dual action anti-HIV peptides
oaire.awardTitleInnovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training , and communication.
oaire.awardTitleTowards the development of antimicrobial peptides active against bacterial biofilms
oaire.awardTitleTargeting brain-resident viruses across the blood-brain barrier using peptide drugs.
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQEQ-MED%2F4412%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/644167/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114425%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F136752%2F2018/PT
oaire.citation.issue8pt_PT
oaire.citation.titleJournal of Peptide Sciencept_PT
oaire.citation.volume25pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamH2020
oaire.fundingStreamOE
person.familyNameDias
person.familyNameMendonça
person.familyNameCastanho
person.familyNameVeiga
person.givenNameSusana
person.givenNameDiogo
person.givenNameMiguel
person.givenNameAna Salome
person.identifier.ciencia-idF61D-0A28-659A
person.identifier.ciencia-id2F1E-8D99-DA70
person.identifier.orcid0000-0001-8910-5404
person.identifier.orcid0000-0001-8003-4662
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-9892-2243
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id56745037100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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