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Anti-platelet activity of a three-finger toxin (3FTx) from Indian monocled cobra (Naja kaouthia) venom
Authors:Chandrasekhar Chanda  Angshuman Sarkar  Srinivas Sistla  Dibakar Chakrabarty
Institution:1. Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K.K. Birla Goa Campus, Zuarinagar, Goa 403726, India;2. GE Healthcare Life Sciences, John F. Welch Technology Centre, EPIP, Phase 2, Whitefield Road, Bangalore, India
Abstract:A low molecular weight anti-platelet peptide (6.9 kDa) has been purified from Naja kaouthia venom and was named KT-6.9. MALDI-TOF/TOF mass spectrometry analysis revealed the homology of KT-6.9 peptide sequence with many three finger toxin family members. KT-6.9 inhibited human platelet aggregation process in a dose dependent manner. It has inhibited ADP, thrombin and arachidonic acid induced platelet aggregation process in dose dependent manner, but did not inhibit collagen and ristocetin induced platelet aggregation. Strong inhibition (70%) of the ADP induced platelet aggregation by KT-6.9 suggests competition with ADP for its receptors on platelet surface. Anti-platelet activity of KT-6.9 was found to be 25 times stronger than that of anti-platelet drug clopidogrel. Binding of KT-6.9 to platelet surface was confirmed by surface plasma resonance analysis using BIAcore X100. Binding was also observed by a modified sandwich ELISA method using anti-KT-6.9 antibodies. KT-6.9 is probably the first 3FTx from Indian monocled cobra venom reported as a platelet aggregation inhibitor.
Keywords:ADP  adenosine di-phosphate  FITC  fluorescein isothiocyanate  GPCR  G-protein coupled receptor  MW  molecular weight  RP-HPLC  reversed phase high performance liquid chromatography  SPR  surface plasma resonance
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