Abstract
BackgroundVenoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The bradykinin-potentiating peptides (BPPs) comprise a class of angiotensin-I converting enzyme (ACE) inhibitors. The BPPs usually consist of oligopeptides with 5 to 13 residues with a high number of proline residues and the tripeptide Ile-Pro-Pro (IPP-tripeptide) in the C-terminus region and have a conserved N-terminal pyroglutamate residue. As a whole, the action of the BPPs on prey and snakebite victims results in the decrease of the blood pressure. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros.MethodsThe crude venom of B. g. rhinoceros was fractionated by size exclusion chromatography and the peptide fraction (<7 kDa) was separated by reverse phase chromatography (RP-HPLC) and analyzed by ESI-IT-TOF-MS/MS. One new BPP was identified, synthetized and assayed for ACE inhibition and, in vivo, for edema potentiation.ResultsTypical BPP signatures were identified in three RP-HPLC fractions. CID fragmentation presented the usual y-ion of the terminal P-P fragment as a predominant signal at m/z 213.1. De novo peptide sequencing identified one Bothrops-like BPP and one new BPP sequence. The new BPP was synthesized and showed poor inhibition over ACE, but displayed significant bradykinin-induced edema potentiation.ConclusionsSo far, few BPPs are described in Viperinae, and based on the sequenced peptides, two non-canonical sequences were detected. The possible clinical role of this new peptides remains unclear.
Highlights
Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective
We describe the sequence of two Bradykinin-potentiating peptide (BPP) isolated from the venom of Bitis gabonica rhinoceros and present an in vivo functional characterization of the synthetic analogue
The fragmentation of BPPs by collision-induced dissociation during electrospray tandem mass spectrometry analysis (ESI-Mass spectrometry (MS)/MS) generates a predominant signal at m/z 213.1 corresponding to the y-ion of the terminal Pro–Pro fragment [25]
Summary
Venoms represent a still underexplored reservoir of bioactive components that might mitigate or cure diseases in conditions in which conventional therapy is ineffective. The aim of this work was to isolate and characterize novel BPPs from the venom of Bitis gabonica rhinoceros. Snake venoms are a complex mixture of peptides and proteins, including peptidases. Many of these toxins mimic structurally and functionally endogenous molecules of the prey involved in homeostatic processes, escaping, from the regulation mechanisms, disturbing physiological equilibrium. The somatic ACE is a dipeptidyl carboxypeptidase situated on the external surface of endothelial cells. This enzyme plays a central role in blood pressure regulation, is composed of two highly similar domains, the N- and Cdomains [14]. The C-domain of mammalian ACE is mainly responsible for Ang II formation while BK is inactivated by both domains with the same efficiency [18]
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