A new peptide (Ruviprase) purified from the venom of Daboia russelii russelii shows potent anticoagulant activity via non-enzymatic inhibition of thrombin and factor Xa
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Title |
A new peptide (Ruviprase) purified from the venom of Daboia russelii russelii shows potent anticoagulant activity via non-enzymatic inhibition of thrombin and factor Xa
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Creator |
THAKUR, R
KUMAR, A BOSE, B PANDA, D SAIKIA, D CHATTOPADHYAY, P MUKHERJEE, AK |
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Subject |
Anticoagulant peptide
Biosensor analysis Daboia russelii russelii Factor Xa inhibitor Protein-protein interaction Thrombin inhibitor SERINE-PROTEASE INHIBITOR VIPER VENOM BOOPHILUS-MICROPLUS CATTLE TICK BOTHROJARACIN PHARMACODYNAMICS ANTITHROMBIN MEDICINE THERAPY CLONING |
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Description |
Compounds showing dual inhibition of thrombin and factor Xa (FXa) are the subject of great interest owing to their broader specificity for effective anticoagulation therapy against cardiovascular disorders. This is the first report on the functional characterization and assessment of therapeutic potential of a 4423.6 Da inhibitory peptide (Ruviprase) purified from Daboia russelii russelii venom. The secondary structure of Ruviprase is composed of a-helices (61.9%) and random coils (38.1%). The partial N-terminal sequence (E-1-V-2-X-3-W-4-W-5-W-6-A(7)-Q(8)-L-9-S-10) of Ruviprase demonstrated significant similarity (80.0%) with an internal sequence of apoptosis-stimulating protein reported from the venom of Ophiophagus hannah and Python bivittatus; albeit Ruviprase did not show sequence similarity with existing thrombin/FXa inhibitors, suggestingits uniqueness. Ruviprase demonstrated a potent in vitro anticoagulant property and inhibited both thrombin and FXa following slow binding kinetics. Ruviprase inhibited thrombin by binding to its active site via an uncompetitive mechanism with a Ki value and dissociation constant (K-D) of 0.42 mu M and 0.46 mu M, respectively. Conversely, Ruviprase demonstrated mixed inhibition (Ki = 0.16 mu M) of FXa towards its physiological substrate prothrombin. Furthermore, the biological properties of Ruviprase could not be neutralized by commercial polyvalent or monovalent antivenom. Ruviprase at a dose of 2.0 mg/kg was non-toxic and showed potent in vivo anticoagulant activity after 6 h of intraperitoneal treatment in mice. Because of the potent anticoagulant property as well as non-toxic nature of Ruviprase, the possible application of the peptide as an antithrombotic agent for combating thrombosis-associated ailments appears promising. (C) 2014 Elsevier Masson SAS. All rights reserved.
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Publisher |
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
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Date |
2014-12-28T14:47:52Z
2014-12-28T14:47:52Z 2014 |
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Type |
Article
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Identifier |
BIOCHIMIE, 105C149-158
0300-9084 1638-6183 http://dx.doi.org/10.1016/j.biochi.2014.07.006 http://dspace.library.iitb.ac.in/jspui/handle/100/16792 |
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Language |
English
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