Paramagnetic bradykinin analogues as substrates for angiotensin I-converting enzyme: Pharmacological and conformation studies

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dc.citation.volume69
dc.contributor.authorTeixeira, Luis Gustavo de Deus [UNIFESP]
dc.contributor.authorMalavolta, Luciana
dc.contributor.authorBersanetti, Patricia Alessandra [UNIFESP]
dc.contributor.authorSchreier, Shirley
dc.contributor.authorCarmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.authorNakaie, Clovis Ryuichi [UNIFESP]
dc.coverageSan Diego
dc.date.accessioned2020-07-31T12:47:13Z
dc.date.available2020-07-31T12:47:13Z
dc.date.issued2016
dc.description.abstractThis study uses EPR, CD, and fluorescence spectroscopy to examine the structure of bradykinin (BK) analogues attaching the paramagnetic amino acid-type Toac (2,2,6,6-tetramethylpiperidine-1-oxyl-4-a mino-4-carboxylic acid) at positions 0, 3, 7, and 9. The data were correlated with the potencies in muscle contractile experiments and the substrate properties towards the angiotensin I-converting enzyme (ACE). A study of the biological activities in guinea pig ileum and rat uterus indicated that only Toac(0)-BK partially maintained its native biological potency among the tested peptides. This and its counterpart, Toac3-BK, maintained the ability to act as ACE substrates. These results indicate that peptides bearing Toac probe far from the ACE cleavage sites were more susceptible to hydrolysis by ACE. The results also emphasize the existence of a finer control for BK-receptor interaction than for BK binding at the catalytic site of this metallodipetidase. The kinetic kcat/ Km values decreased from 202.7 to 38.9 mu M-1 min(-1) for BK and Toac3-BK, respectively. EPR, CD, and fluorescence experiments reveal a direct relationship between the structure and activity of these paramagnetic peptides. In contrast to the turn-folded structures of the Toac-internally labeled peptides, more extended conformations were displayed by N-or C-terminally Toac-labeled analogues. Lastly, this work supports the feasibility of monitoring the progress of the ACE-hydrolytic process of Toac-attached peptides by examining time-dependent EPR spectral variations. (C) 2016 Elsevier Inc. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationSanta Casa Sao Paulo Sch Med Sci, Dept Physiol Sci, BR-01221020 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Hlth Informat, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Chem, Dept Biochem, BR-05513970 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespDepartment of Biophysics, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, 04044-020 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespDepartment of Health Informatics, Universidade Federal de Sao Paulo, 04023-062 Sao Paulo, SP, 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.format.extent159-166
dc.identifierhttp://dx.doi.org/10.1016/j.bioorg.2016.10.006
dc.identifier.citationBioorganic Chemistry. San Diego, v. 69, p. 159-166, 2016.
dc.identifier.doi10.1016/j.bioorg.2016.10.006
dc.identifier.issn0045-2068
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56675
dc.identifier.wosWOS:000387978900017
dc.language.isoeng
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofBioorganic Chemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectBradykininen
dc.subjectAngiotensin I-converting enzymeen
dc.subjectACEen
dc.subjectToacen
dc.subjectSpin labelen
dc.subjectBiological activityen
dc.titleParamagnetic bradykinin analogues as substrates for angiotensin I-converting enzyme: Pharmacological and conformation studiesen
dc.typeinfo:eu-repo/semantics/article
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