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Biochim Biophys Acta. 2015 Jun;1850(6):1180-7. doi: 10.1016/j.bbagen.2015.02.005. Epub 2015 Feb 14.

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

Author information

1
Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil.
2
Special Laboratory of Applied Toxinology/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, SP, Brazil.
3
Department of Biochemistry, Federal University of São Paulo, São Paulo, Brazil.
4
Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil.
5
Department of Pharmacology, University of São Paulo, São Paulo, Brazil.
6
Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil. Electronic address: fernanda.portaro@butantan.gov.br.

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 Bitis 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 Bitis gabonica gabonica, Bitis nasicornis, Bitis 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 proline-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 proline-rich peptides, also known as bradykinin-potentiating peptides. Four synthetic peptides indicated a preferential inhibition of angiotensin-converting enzyme C-domain. In vivo studies show that the proline-rich oligopeptides are hypotensive molecules.

GENERAL SIGNIFICANCE:

Although proline-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 Bitis spp, who display severe hypotension.

KEYWORDS:

Angiotensin-converting enzyme (ACE); Bitis; Bradykinin-potentiating peptide (BPP); Hypotension; Proline-rich oligopeptide (PRO); Venom

PMID:
25688758
DOI:
10.1016/j.bbagen.2015.02.005
[Indexed for MEDLINE]
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