Abstract
BackgroundSnake venom is a source of many pharmacologically important molecules. Agkistrodon bilineatus commonly known as Cantil, is spread over Central America particularly in Mexico and Costa Rica. From the venom of Agkistrodon bilineatus we have isolated and characterised six hypotensive peptides, and two bradykinin inhibitor peptides. The IC-50 value of four synthesized peptides was studied, towards angiotensin converting enzyme, in order to study the structure-function relationship of these peptides.ResultsThe purification of the peptides was carried out by size exclusion chromatography, followed by reverse phase chromatography. Sequences of all peptides were determined applying MALDI-TOF/TOF mass spectrometry. These hypotensive peptides bear homology to bradykinin potentiating peptides and venom vasodilator peptide. The peptide with m/z 1355.53 (M + H)+1, and the corresponding sequence ZQWAQGRAPHPP, we identified for the first time. A precursor protein containing a fragment of this peptide was reported at genome level, (Uniprot ID P68515), in Bothrops insularis venom gland. These proline rich hypotensive peptides or bradykinin potentiating peptides are usually present in the venom of Crotalinae, and exhibit specificity in binding to the C domain of somatic angiotensin converting enzyme. Four of these hypotensive peptides, were selected and synthesized to obtain the required quantity to study their IC50 values in complex with the angiotensin converting enzyme. The peptide with the sequence ZLWPRPQIPP displayed the lowest IC50 value of 0.64 μM. The IC50 value of the peptide ZQWAQGRAPHPP was 3.63 μM.ConclusionThe canonical snake venom BPPs classically display the IPP motif at the C-terminus. Our data suggest that the replacement of the highly conserved hydrophobic isoleucine by histidine does not affect the inhibitory activity, indicating that isoleucine is not mandatory to inhibit the angiotensin converting enzyme. The evaluation of IC 50 values show that the peptide with basic pI value exhibits a lower IC 50 value.
Highlights
Snake venom is a source of many pharmacologically important molecules
The activity of the material corresponding to each peak was again tested for inhibitory activity towards the angiotensin converting enzyme and all peptides corresponding to the peaks 1 to 4 (Fig. 2) were found to inhibit the angiotensin converting enzyme
The Bradykinin potentiating peptides (BPP) isolated and characterized within this work show homology with BPPs already isolated from other snake venoms
Summary
Snake venom is a source of many pharmacologically important molecules. Agkistrodon bilineatus commonly known as Cantil, is spread over Central America in Mexico and Costa Rica. From the venom of Agkistrodon bilineatus we have isolated and characterised six hypotensive peptides, and two bradykinin inhibitor peptides. Snake venom is known for its toxic and lethal effects in its prey. Nature has endowed this creature, with this special secretion to survive in a particular niche [1]. Bradykinin potentiating peptides (BPP) are a good example in this respect. These peptides were isolated from the venom of Bothrops jararaca [11]. Captopril, which was the first orally active inhibitor of the angiotensin converting enzyme was designed based on the structure of BPPs isolated from Bothhrops jararaca venom [12]. For example it was shown that the peptide Bj-PRO-10c [19] inhibits ACE, argininosuccinate synthetase, present in the kidney cytosol is its primary target [15, 19,20,21]
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