Identification of novel bradykinin-potentiating peptides and C-type natriuretic peptide from Lachesis muta venom

Snake venomics of the South and Central American Bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis

“…7). BPPs found in fractions Ls7, Lm9/Ls6, Lm6/Ls5, and Lm10/Ls8 have been previously identified by MALDI-TOF MS in the crude venom of a specimen kept in captivity at the serpentarium of the Fundação Ezequiel Dias (Belo Horizonte, Brazil) [35], indicating that expression of these peptides appear not to exhibit geographical variation. BPPs have been described as snake venom inhibitors of the angiotensin-converting enzyme, a dipeptidylcarboxypeptidase expressed in endothelial, epithelial and neuroepithelial cells, which converts inactive angiotensin I into the potent vasoconstrictor angiotensin II, and degrades bradykinin into bradykinin (1-7) or bradykinin (1-5) [36].…”

Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution

“…In fact, there are two almost identical cDNAs differing by a few nucleotides, each one containing half of the total ESTs, suggesting two expressed alleles. The prototypical BPP precursor found here contains five BPPs (Lm-BPP 1-5) interspersed with spacers, plus the 22-amino-acidlong CNP at the C terminus, and was further studied by means of resequencing the cDNAs characterized from the venom and is described elsewhere (Soares et al 2005). The remarkable feature is that Lm-BPP 1 is unique because it was shown by matrix-assisted laser desorption ionization time-of-flight mass spectrometry to be processed at the N terminus, being three residues shorter than that expected from the cDNA, beginning with a Trp at the N terminus (Soares et al 2005), whereas all other purified BPPs have a N-terminal Gln residue that is circularized to pyroglutamate (Higuchi et al 1999).…”

“…Most probably there is a differential regulation of BPP mRNA expression and/or turnover in the steady state, since no other studies reported such an expression level of BPP mRNA in stimulated venom glands. The peptides secreted to the venom may or may not be at the same abundance, but these data and the presence of an unusually processed BPP at the venom (Soares et al 2005) suggest an important contribution of this component to the known hypotensive effect of the venom ( Jorge et al 1997). The overall occurrence of the other toxins is consistent with that observed in the Viperidae transcriptomes cited above.…”

Venomics as a drug discovery platform

“…However, contrary to proteomics studies in which uninterpreted tandem MS spectra are searched against a database of proteins in a 'bottom-up' approach, in organisms with unknown genomes, true de novo peptide sequencing is necessary in a 'top-down' approach. Approaches involving collision-induced dissociation were used in the characterization of conotoxins, from Conus monile and Conus virgo [16], and small snake peptides, such as BPPs [17], poly-His and poly-Gly peptides [18] and sarafotoxins [19]. These last results emphasize the increasing role of Fourier-transform ion cyclotron resonance MS, which brings high resolution and mass accuracy to de novo sequencing, allowing the unambiguous assignment of fragment masses and quasi-isobaric residues, such as lysine and glutamine, which differ by only 0.003638 Da.…”