Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor

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dc.contributor.authorCoppini, Larissa Pereira [UNIFESP]
dc.contributor.authorBarros, Nilana M. T. [UNIFESP]
dc.contributor.authorOliveira, Marcela [UNIFESP]
dc.contributor.authorHirata, Izaura Y. [UNIFESP]
dc.contributor.authorAlves, Marcio F. M. [UNIFESP]
dc.contributor.authorPaschoalin, Thaysa [UNIFESP]
dc.contributor.authorAssis, Diego M. [UNIFESP]
dc.contributor.authorJuliano, Maria A. [UNIFESP]
dc.contributor.authorPuzer, Luciano
dc.contributor.authorBroemme, Dieter
dc.contributor.authorCarmona, Adriana K. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Triangulo Mineiro
dc.contributor.institutionUniv British Columbia
dc.date.accessioned2016-01-24T13:59:40Z
dc.date.available2016-01-24T13:59:40Z
dc.date.issued2010-05-01
dc.description.abstractPlasminogen is a glycoprotein implicated in angiogenesis and fibrin clot degradation associated with the release of angiostatin and plasmin activation, respectively We have recently reported that cathepsin V. but not cathepsins L. B, and K. can release angiostatin-like fragments from plasminogen. Here, we extended the investigation to cathepsin S which has been implicated in angiogenesis and tumor cell proliferation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of plasminogen hydrolysis by cathepsin S revealed generation of two fragments (60 and 38 kDa). Amino-terminal sequencing indicated that cleavage occurs at the Leu469-Leu470 peptide bond. in contrast to cathepsin V, which possesses antiangiogenic activity, cathepsin S plasminogen cleavage products were not capable of inhibiting angiogenesis on endothelial cells. Moreover, we explored the different selectivities presented by cathepsins V and S towards plasminogen and synthesized fluorescence resonance energy transfer peptides encompassing the hydrolyzed peptide bonds by both enzymes. the peptide Abz-VLFEKKQ-EDDnp (Abz=ortho-aminobenzoic acid; EDDnp=N-[2,4-dinitrophenyl]ethylenediamine), hydrolyzed by cathepsin V at the Phe-Glu bond. is a selective substrate for the enzyme when compared with cathepsins B. L, and S, whereas Abz-VLFEKKVYLQ-EDDnp is an efficient cathepsin L inhibitor. the demonstrated importance of the S-3'-P-3' interaction indicates the significance of the extended subsites for enzyme specificity and affinity.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Fed Triangulo Mineiro, Dept Biol Sci, BR-38025015 Uberaba, MG, Brazil
dc.description.affiliationUniv British Columbia, Dept Dent, Vancouver, BC V6T 1Z3, Canada
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCanada Research Chair Award
dc.format.extent561-570
dc.identifierhttp://dx.doi.org/10.1515/BC.2010.049
dc.identifier.citationBiological Chemistry. Berlin: Walter de Gruyter Gmbh, v. 391, n. 5, p. 561-570, 2010.
dc.identifier.doi10.1515/BC.2010.049
dc.identifier.issn1431-6730
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32535
dc.identifier.wosWOS:000277536500010
dc.language.isoeng
dc.publisherWalter de Gruyter Gmbh
dc.relation.ispartofBiological Chemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectangiostatinen
dc.subjectcathepsin Len
dc.subjectcathepsin Sen
dc.subjectcathepsin Ven
dc.subjectfluorescence resonance energy transfer peptidesen
dc.subjectplasminogenen
dc.titlePlasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitoren
dc.typeinfo:eu-repo/semantics/article
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