Isolation and biochemical characterization of bradykinin-potentiating peptides from Bitis gabonica rhinocerosReportar como inadecuado




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Journal of Venomous Animals and Toxins including Tropical Diseases

, 23:33

Hyphenated mass spectrometry strategies as tools for unveiling peptide toxins with potential therapeutic application

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.

KeywordsPeptide Hypotension Viperinae AbbreviationsACEAngiotensin-I converting enzyme

Ang IIAngiotensin II

BKBradykinin

BPPBradykinin-potentiating peptide

FRETFluorescence resonance energy transfer

MSMass spectrometry

MS1 Generation product ion spectra

MS2 Generation product ion spectra

MS3 Generation product ion spectra

SECSize exclusion chromatography

TFATrifluoroacetic acid

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Autor: Tamara M. Fucase - Juliana M. Sciani - Ingrid Cavalcante - Vincent L. Viala - Bruno B. Chagas - Daniel C. Pimenta - Pat

Fuente: https://link.springer.com/







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