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Synthesis, structure, and activity of the antifungal plant defensin PvD1

2020Artigo científico Acesso restrito
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dc.contributor.authorSkalska, Julia
dc.contributor.authorAndrade, Vitor M.
dc.contributor.authorCena, Gabrielle L.
dc.contributor.authorHarvey, Peta J.
dc.contributor.authorGaspar, Diana
dc.contributor.authorMello, Érica O.
dc.contributor.authorHenriques, Sónia T.
dc.contributor.authorValle, Javier
dc.contributor.authorGomes, Valdirene M.
dc.contributor.authorConceição, Katia
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorAndreu, David
dc.date.accessioned2023-05-09T14:15:14Z
dc.date.available2023-05-09T14:15:14Z
dc.date.issued2020
dc.descriptionCopyright © 2020 American Chemical Societypt_PT
dc.description.abstractAvailable treatments for invasive fungal infections have limitations, including toxicity and the emergence of resistant strains. Therefore, there is an urgent need for alternative solutions. Because of their unique mode of action and high selectivity, plant defensins (PDs) are worthy therapeutic candidates. Chemical synthesis remains a preferred method for the production of many peptide-based therapeutics. Given the relatively long sequence of PDs, as well as their complicated posttranslational modifications, the synthetic route can be considered challenging. Here, we describe a total synthesis of PvD1, the defensin from the common bean Phaseolus vulgaris. Analytical, structural, and functional characterization revealed that both natural and synthetic peptides fold into a canonical CSαβ motif stabilized by conserved disulfide bonds. Moreover, synthetic PvD1 retained the biological activity against four different Candida species and showed no toxicity in vivo. Adding the high resistance of synthetic PvD1 to proteolytic degradation, we claim that conditions are now met to consider PDs druggable biologicals.pt_PT
dc.description.sponsorshipThis project was supported by a Marie Skłodowska-Curie Research and Innovation Staff Exchange grant (RISE; call: H2020-MSCA-RISE-2014, grant agreement 644167). Work at UPF was supported by grant AGL2017-84097-C2-2-R and the “Marı́a de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0370) from the Spanish Ministry of Economy and Competitiveness (MINECO). The authors thank Fundação para a Ciência e a Tecnologia (FCT I.P., Portugal) for funding: PTDC/BBB-BQB/1693/2014 and Brazilian agencies CNPq (305495/2017-8), FAPERJ (E-26/203090/2016; 26/202.132/2015), and FAPESP (2017/00032-0). J.S. and D.G. would like to acknowledge FCT I.P. for fellowships: PD/BD/114177/2016 and SFRH/BPD/109010/2015. S.T.H. is an Australian Research Council (ARC) Future Fellow (FT150100398).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ. Med. Chem. 2020, 63, 9391−9402pt_PT
dc.identifier.doi10.1021/acs.jmedchem.0c00543pt_PT
dc.identifier.eissn1520-4804
dc.identifier.issn0022-2623
dc.identifier.urihttp://hdl.handle.net/10451/57392
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherACS Publicationspt_PT
dc.relationInnovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training , and communication.
dc.relationCell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment
dc.relationBiophysical studies tounravel the mechanism of action of anticancer peptides
dc.relationCell-cell direct/indirect communication in metastatic breast cancer as a control point in oncotherapy
dc.relation.publisherversionhttps://pubs.acs.org/journal/jmcmarpt_PT
dc.titleSynthesis, structure, and activity of the antifungal plant defensin PvD1pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleInnovative peptides against cancer and pathogenic bacteria, with advances in science, biopharmaceutical drug development, product market targeting, training , and communication.
oaire.awardTitleCell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment
oaire.awardTitleBiophysical studies tounravel the mechanism of action of anticancer peptides
oaire.awardTitleCell-cell direct/indirect communication in metastatic breast cancer as a control point in oncotherapy
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/644167/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBBB-BQB%2F1693%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F114177%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F109010%2F2015/PT
oaire.citation.endPage9402pt_PT
oaire.citation.issue17pt_PT
oaire.citation.startPage9391pt_PT
oaire.citation.titleJournal of Medicinal Chemistrypt_PT
oaire.citation.volume63pt_PT
oaire.fundingStreamH2020
oaire.fundingStream3599-PPCDT
person.familyNameSkalska
person.familyNameGaspar
person.familyNameCastanho
person.givenNameJulia
person.givenNameDiana
person.givenNameMiguel
person.identifier103438
person.identifier.orcid0000-0001-8129-4095
person.identifier.orcid0000-0002-9602-567X
person.identifier.orcid0000-0001-7891-7562
person.identifier.ridM-9562-2015
person.identifier.scopus-author-id55180303000
person.identifier.scopus-author-id56605575600
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.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
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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relation.isAuthorOfPublication9fe9e286-d492-4b04-b6ba-5b214f661b7f
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relation.isAuthorOfPublication.latestForDiscovery9fe9e286-d492-4b04-b6ba-5b214f661b7f
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