کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8305229 | 1538425 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
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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کلمات کلیدی
PBSantithrombin-IIISGPTSGOTRVVFXaPolyvalent antivenomCK-MBPLA2PaVTFAPNAPPPMAVAT-IIIp-Nitroanilide - p-nitroanilideALP - آلکالن فسفاتازAlkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییphospholipase A2 - آنزیم فسفولیپاز A2 Basic Local Alignment Search Tool - ابزار جستجوی محلی سازگاری محلیblastp - انفجارSerum glutamic oxaloacetic transaminase - ترانس آمیناز اگزوالکتیک گلوتامین سرمserum glutamic pyruvic transaminase - ترانس آمیناز پریوویک گلوتامین سرمProtein–protein interaction - تعامل پروتئین-پروتئینRussell's viper venom - جاذبه روسل راسcircular dichroism - رنگ تابی دورانیFactor Xa - فاکتور XaPhosphate buffered saline - فسفات بافر شورthrombin inhibitor - مهار کننده ترومبینfactor Xa inhibitor - مهار کننده فاکتور XaResponse unit - واحد پاسخplatelet poor plasma - پلاکت پلاسمای ضعیفoptical density - چگالی نوریCreatine kinase - کراتین کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 α-helices (61.9%) and random coils (38.1%). The partial N-terminal sequence (E1-V2-X3-W4-W5-W6-A7-Q8-L9-S10) 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, suggesting its 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 (KD) of 0.42 μM and 0.46 μM, respectively. Conversely, Ruviprase demonstrated mixed inhibition (Ki = 0.16 μM) 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 105, October 2014, Pages 149-158
Journal: Biochimie - Volume 105, October 2014, Pages 149-158
نویسندگان
Rupamoni Thakur, Ashok Kumar, Biplab Bose, Dulal Panda, Debashree Saikia, Pronobesh Chattopadhyay, Ashis K. Mukherjee,