Background:
Cerastes cerastes venom contains several bioactive proteins with inhibitory potential of platelet
aggregation and blood coagulation.
Material and Methods:
The purification process consists of three successive chromatographies including G75-Sephadex
size exclusion, DEAE exchange chromatography and affinity using Sildenafil as a main PDEs’ specific inhibitor. The amino
acid sequence of purified Cc-PDE was determined by liquid chromatography coupled off line to MALDI-TOF/TOF. Modeling and structural features were obtained using several bioinformatics tools. In vivo and in vitro antiplatelet aggregation and
anticoagulant assays were performed.
Results:
Cc-PDE (73 506.42 Da) is a 654-residue single polypeptide with 1-22 signal peptide and it ischaracterized by the
presence of predominant basic amino acids suitable to alkaline pI (8.17). Cc-PDE structure is composed of β-strands (17%)
and α-helices (24%) and it shares a high identity with homologous snake venom PDEs. Cc-PDE hydrolyzes both Bis-pnitrophenyl phosphate (Km = 2.60 ± 0.95 mM, Vmax = 0.017 ± 0.002569 µmolmin-1
) and p-nitrophenyl phosphate (Km =
7.13 mM ± 0.04490 mM, Vmax = 0.053 ±0.012 µmolmin-1
). Cc-PDE prevents ADP- and ATP-induced platelet aggregation
by hydrolyzing ADP and ATP, reducing surface P-selectin expression and attenuating platelet function. In addition, Cc-PDE
inhibits coagulation factors involved in the intrinsic pathway demonstrated by a significant prolongation of activated partial
thromboplastin time and in vivo long-lasting anticoagulation.
Conclusion:
The obtained results revealed that Cc-PDE may have a therapeutic potential and could be a remedy for thromboembolic diseases as an alternative of anticoagulant and antiplatelet aggregation chemical origins.
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