Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

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dc.citation.issue1
dc.citation.volume6
dc.contributor.authorQvit, Nir
dc.contributor.authorSchechtman, Deborah
dc.contributor.authorPena, Darlene Aparecida
dc.contributor.authorBerti, Denise Aparecida
dc.contributor.authorSoares, Chrislaine Oliveira
dc.contributor.authorMiao, Qianqian
dc.contributor.authorLiang, Liying (Annie)
dc.contributor.authorBaron, Lauren A.
dc.contributor.authorTeh-Poot, Christian
dc.contributor.authorMartinez-Vega, Pedro
dc.contributor.authorRamirez-Sierra, Maria Jesus
dc.contributor.authorChurchill, Eric
dc.contributor.authorCunningham, Anna D.
dc.contributor.authorMalkovskiy, Andrey V.
dc.contributor.authorFederspiel, Nancy A.
dc.contributor.authorGozzo, Fabio Cesar
dc.contributor.authorTorrecilhas, Ana Claudia [UNIFESP]
dc.contributor.authorManso Alves, Maria Julia
dc.contributor.authorJardim, Armando
dc.contributor.authorMomar, Ndao
dc.contributor.authorDumonteil, Eric
dc.contributor.authorMochly-Rosen, Daria
dc.coverageOxford
dc.date.accessioned2020-07-22T13:23:21Z
dc.date.available2020-07-22T13:23:21Z
dc.date.issued2016
dc.description.abstractParasitic diseases cause similar to 500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosoma receptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.en
dc.description.affiliationStanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA
dc.description.affiliationUniv Sao Paulo, Inst Quim, Dept Bioquim, BR-05508 Sao Paulo, SP, Brazil
dc.description.affiliationMcGill Univ, Res Inst, Natl Reference Ctr Parasitol, Montreal, PQ, Canada
dc.description.affiliationUniv Autonoma Yucatan, Ctr Invest Reg Dr Hideyo Noguchi, Parasitol Lab, Merida, Yucatan, Mexico
dc.description.affiliationStanford Univ, Biomat & Adv Drug Delivery Lab, Stanford, CA 94305 USA
dc.description.affiliationUniv Estadual Campinas, Inst Chem, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Ciencias Biol, Campus Diadema, Sao Paulo, Brazil
dc.description.affiliationMcGill Univ, Inst Parasitol, Quebec City, PQ, Canada
dc.description.affiliationMcGill Univ, Ctr Host Parasite Interact, Quebec City, PQ, Canada
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Ciencias Biol, Campus Diadema, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipIDNIH: TW008781-01C-IDEA
dc.description.sponsorshipIDNIH: AI078505
dc.format.extent74-84
dc.identifierhttp://dx.doi.org/10.1016/j.ijpddr.2016.02.003
dc.identifier.citationInternational Journal For Parasitology-Drugs And Drug Resistance. Oxford, v. 6, n. 1, p. 74-84, 2016.
dc.identifier.doi10.1016/j.ijpddr.2016.02.003
dc.identifier.fileWOS000372717200008.pdf
dc.identifier.issn2211-3207
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56191
dc.identifier.wosWOS:000372717200008
dc.language.isoeng
dc.publisherElsevier Sci Ltd
dc.relation.ispartofInternational Journal For Parasitology-Drugs And Drug Resistance
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectChagas diseaseen
dc.subjectLeishmaniasisen
dc.subjectPeptideen
dc.subjectLACKen
dc.subjectTRACKen
dc.subjectScaffold proteinen
dc.titleScaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitorsen
dc.typeinfo:eu-repo/semantics/article
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