Conformational and biological properties of Bauhinia bauhinioides kallikrein inhibitor fragments with bradykinin-like activities

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dc.contributor.authorAlves, Flavio Lopes [UNIFESP]
dc.contributor.authorOliva, Maria Luiza Vilela [UNIFESP]
dc.contributor.authorMiranda, Antonio [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:40:32Z
dc.date.available2016-01-24T14:40:32Z
dc.date.issued2015-06-01
dc.description.abstractProteinase inhibitors extracted form medicinal plants are an interesting source of new drugs. Modifications in the structure of some of this kind of macromolecules could also lead to compounds of interesting biological properties. in this work, we synthesized and tested one fragment containing the reactive site of the Bauhinia bauhinioides kallikrein inhibitor (BbKI), denoted BbKI(51-62), and a related analog (P-2) in which a proline residue was inserted in order to mimic the N-terminal region of the bradykinin molecule. the related retro-inverso counterparts Ri-BbKI(51-62) and Ri-P-2 were also included. the ability of these peptides to induce contraction of stomach fundus isolated from mouse was evaluated as well as their capability to induce calcium release from a cell culture of smooth muscle from guinea pig ileum. the conformational properties of the peptides were evaluated by circular dichroism and their resistance to enzymatic degradation by exposure to human blood plasma. Our results show that neither the parent BbKI(51-62) nor its Ri-BbKI(51-62) analog exhibit bradykinin-like activity, although the retro-inverso isomer was resistant to blood plasma degradation. On the other hand, the peptides P-2 and Ri-P-2 presented contractile activities on gastric smooth muscle from stomach fundus possibly by acting via B-2 receptor. Both compounds also induce calcium release from guinea pig ileum muscle cells in a manner similar to bradykinin. Moreover, both compounds also inhibited porcine pancreatic kallikrein. However, conformational analysis did not reveal any direct correlation between structure and biological effects. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent495-500
dc.identifierhttp://dx.doi.org/10.1002/psc.2766
dc.identifier.citationJournal of Peptide Science. Hoboken: Wiley-Blackwell, v. 21, n. 6, p. 495-500, 2015.
dc.identifier.doi10.1002/psc.2766
dc.identifier.issn1075-2617
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/39115
dc.identifier.wosWOS:000354732200007
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofJournal of Peptide Science
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectbradykininen
dc.subjectbradykinin-like activitiesen
dc.subjectplant inhibitoren
dc.subjectretro-inverso peptidesen
dc.titleConformational and biological properties of Bauhinia bauhinioides kallikrein inhibitor fragments with bradykinin-like activitiesen
dc.typeinfo:eu-repo/semantics/article
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