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Antifungal and anti-biofilm activity of designed derivatives from kyotorphin

dc.contributor.authorMartins de Andrade, Vitor
dc.contributor.authorBardají, Eduard
dc.contributor.authorHeras, Montserrat
dc.contributor.authorRamu, Vasanthakumar G.
dc.contributor.authorJunqueira, Juliana Campos
dc.contributor.authorDiane dos Santos, Jéssica
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorConceição, Katia
dc.date.accessioned2023-05-03T14:58:20Z
dc.date.available2023-05-03T14:58:20Z
dc.date.issued2020
dc.description© 2019 British Mycological Society. Published by Elsevier Ltd. All rights reserved.pt_PT
dc.description.abstractKyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous analgesic neuropeptide first isolated from bovine brain in 1979. Previous studies have shown that kyotorphins possess anti-inflammatory and antimicrobial activity. Six kyotorphins—KTP-NH2, KTP–NH2–DL, ibuprofen-conjugated KTP (IbKTP), IbKTP-NH2, N-methyl-D-Tyr-L-Arg, and N-methyl-L-Tyr-D-Arg—were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. This study assessed the antimicrobial and antibiofilm activity of these peptides. The antifungal activity of kyotorphins was determined in representative strains of Candida species, including Candida albicans ATCC 10231, Candida krusei ATCC 6258, and six clinical isolates—Candida dubliniensis 19-S, Candida glabrata 217-S, Candida lusitaniae 14-S, Candida novergensis 51-S, Candida parapsilosis 63, and Candida tropicalis 140-S—obtained from the oral cavity of HIV-positive patients. The peptides were synthesized by standard solution or solid-phase synthesis, purified by RP-HPLC (purity >95 %), and characterized by nuclear magnetic resonance. The results of the broth microdilution assay and scanning electron microscopy showed that IbKTP-NH2 presented significant antifungal activity against Candida strains and antibiofilm activity against the clinical isolates. The absence of toxic activity and survival after infection was assessed after injecting the peptide in larvae of Galleria mellonella as experimental infection model. Furthermore, IbKTP-NH2 had strong antimicrobial activity against multidrug-resistant bacteria and fungi and was not toxic to G. mellonella larvae up to a concentration of 500 mM. These results suggest that IbKTP-NH2, in addition to its known effect on cell membranes, can elicit a cellular immune response and, therefore, is promising for biomedical application.pt_PT
dc.description.sponsorshipThis research was supported by FAPESP (Grant No. 2017/00032-0). This article is also part of the Fungal Adaptation to Hostile Challenges special issue for the third International Symposium on Fungal Stress (ISFUS), which is supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant No. 2018/20571-6) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Grant No. 88881.289327/2018-01).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.funbio.2019.12.002pt_PT
dc.identifier.eissn1878-6162
dc.identifier.issn1878-6146
dc.identifier.urihttp://hdl.handle.net/10451/57337
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/fungal-biologypt_PT
dc.subjectAnalgesic peptidept_PT
dc.subjectAntibiofilmpt_PT
dc.subjectAntimicrobial peptidespt_PT
dc.subjectToxicitypt_PT
dc.titleAntifungal and anti-biofilm activity of designed derivatives from kyotorphinpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage326pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage316pt_PT
oaire.citation.titleFungal Biologypt_PT
oaire.citation.volume124pt_PT
person.familyNameCastanho
person.givenNameMiguel
person.identifier.orcid0000-0001-7891-7562
person.identifier.scopus-author-id56605575600
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationf5e46f85-fabf-450a-9ee2-1c7b59410892
relation.isAuthorOfPublication.latestForDiscoveryf5e46f85-fabf-450a-9ee2-1c7b59410892

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