New proline-rich oligopeptides from the venom of African adders: Insights into the hypotensive effect of the venoms

New proline-rich oligopeptides from the venom of African adders: Insights into the hypotensive effect of the venoms

Author Kodama, Roberto T. Google Scholar
Cajado-Carvalho, Daniela Google Scholar
Kuniyoshi, Alexandre K. Google Scholar
Kitano, Eduardo S. Google Scholar
Tashima, Alexandre K. Autor UNIFESP Google Scholar
Barna, Barbara F. Google Scholar
Takakura, Ana Carolina Google Scholar
Serrano, Solange M. T. Google Scholar
Dias-Da-Silva, Wilmar Google Scholar
Tambourgi, Denise V. Google Scholar
Portaro, Femanda V. Google Scholar
Institution Butantan Inst
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract Background: the snakes from the Bitis genus are some of the most medically important venomous snakes in sub Saharan Africa, however little is known about the composition and effects of these snake venom peptides. Considering that the victims with Bids genus snakes have exacerbate hypotension and cardiovascular disorders, we investigated here the presence of angiotensin-converting enzyme modulators on four different species of venoms.Methods: the peptide fractions from Bids gabonica gabonica, Bids nasicornis, Bids gabonica rhinoceros and Bitis arietans which showed inhibitory activity on angiotensin-converting enzyme were subjected to mass spectrometry analysis. Eight proline-rich peptides were synthetized and their potencies were evaluated in vitro and in vivo.Results: the MS analysis resulted in over 150 sequences, out of which 32 are new praline-rich oligopeptides, and eight were selected for syntheses. for some peptides, inhibition assays showed inhibitory potentials of cleavage of angiotensin I ten times greater when compared to bradykinin. in vivo tests showed that all peptides decreased mean arterial pressure, followed by tachycardia in 6 out of 8 of the tests.Conclusion: We describe here some new and already known praline-rich peptides, also known as bradykininpotentiating peptides. Four synthetic peptides indicated a preferential inhibition of angiotensin-converting enzyme C-domain. in vivo studies show that the praline-rich oligopeptides are hypotensive molecules.General significance: Although praline-rich oligopeptides are known molecules, we present here 32 new sequences that are inhibitors of the angiotensin-converting enzyme and consistent with the symptoms of the victims of Bids spp, who display severe hypotension. (C) 2015 Elsevier B.V. All rights reserved.
Keywords Bitis
Venom
Praline-rich oligopeptide (PRO)
Bradykinin-potentiating peptide (BPP)
Angiotensin-converting enzyme (ACE)
Hypotension
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number CAPES: 63/2010
FAPESP: 2012/06677-0
Date 2015-06-01
Published in Biochimica Et Biophysica Acta-general Subjects. Amsterdam: Elsevier B.V., v. 1850, n. 6, p. 1180-1187, 2015.
ISSN 0304-4165 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1180-1187
Origin http://dx.doi.org/10.1016/j.bbagen.2015.02.005
Access rights Closed access
Type Article
Web of Science ID WOS:000353736100009
URI http://repositorio.unifesp.br/handle/11600/39122

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