Conformational studies of TOAC-labeled bradykinin analogues in model membranes

Página do item simplificado
dc.contributor.authorVieira, Renata de Freitas Fischer [UNIFESP]
dc.contributor.authorCasallanovo, Fabio
dc.contributor.authorCilli, Eduardo Maffud [UNIFESP]
dc.contributor.authorPaiva, Antonio Cechelli de Mattos [UNIFESP]
dc.contributor.authorSchreier, Shirley
dc.contributor.authorNakaie, Clovis Ryuichi [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T12:33:12Z
dc.date.available2016-01-24T12:33:12Z
dc.date.issued2002-01-01
dc.description.abstractSpin-labeled analogues of bradykinin (BK) were synthesized containing the amino acid TOAC ( 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) either before Arg(1) (TOAC(0)-BK) or replacing Pro(3) (TOAC(3)-BK). Whereas the latter is inactive, the former retains about 70% of BK's activity in isolated rat uterus. A combined electron paramagnetic resonance (EPR)-circular dichroism ( CD) approach was used to examine the conformational properties of the peptides in the presence of membrane-mimetic systems ( negatively charged sodium dodecyl sulfate, SDS, and zwitterionic N-hexadecyl-N, N-dimethyl-3-ammonio-1-propanesulfonate, HPS). While the peptides bind to both monomeric and micellar SDS, no interaction occurs with HPS, evincing the contribution of electrostatic interactions. TOAC(3)-BK's EPR spectral lineshapes are broader than those of TOAC(0)-BK, indicating a more restricted degree of motion at position 3. Moreover, the motional freedom of both peptides decreased upon binding to SDS. BK and TOAC(0)-BK solution CD spectra indicate highly flexible conformations ( possibly an equilibrium between rapidly interconverting forms), while TOAC(3)-BK's spectra correspond to a more ordered structure. SDS binding induces drastic changes in BK and TOAC(0)-BK spectra, indicating stabilization of similar folds. the micelle interface promotes a higher degree of secondary structure by favoring intramolecular hydrogen bonds. in contrast, TOAC(3)-BK spectra remain essentially unchanged. These results are interpreted as due to TOAC's ring imposing a more constrained conformation. This rigidity is very likely responsible for the inability of TOAC(3)-BK to acquire the correct receptor-bound conformation, leading to loss of biological activity. On the other hand, the greater flexibility of TOAC(0)-BK and the similarity between its conformational behavior and that of the native hormone are probably related to their similar biological activity.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Dept Biochem, Inst Chem, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent83-89
dc.identifierhttps://dx.doi.org/10.1023/A:1024130025587
dc.identifier.citationLetters in Peptide Science. Dordrecht: Kluwer Academic Publ, v. 9, n. 2-3, p. 83-89, 2002.
dc.identifier.doi10.1023/A:1024130025587
dc.identifier.issn0929-5666
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/26709
dc.identifier.wosWOS:000183440200005
dc.language.isoeng
dc.publisherKluwer Academic Publ
dc.relation.ispartofLetters in Peptide Science
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectBradykininen
dc.subjectCDen
dc.subjectEPRen
dc.subjectMicelleen
dc.subjectPeptide conformationen
dc.subjectSpin labelen
dc.subjectStructure-activity relationshipen
dc.subjectTOACen
dc.titleConformational studies of TOAC-labeled bradykinin analogues in model membranesen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos