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

作者：Kodama Roberto T; Cajado Carvalho Daniela; Kuniyoshi Alexandre K; Kitano Eduardo S; Tashima Alexandre K; Barna Barbara F; Takakura Ana Carolina; Serrano Solange M T; Dias Da Silva Wilmar; Tambourgi Denise V; Portaro Femanda V^*

来源：Biochimica et Biophysica Acta-General Subjects, 2015, 1850(6): 1180-1187.

DOI：10.1016/j.bbagen.2015.02.005

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

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.

• 出版日期2015-6