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Projects / Programmes source: ARIS

Proteins of the long-nosed viper venom acting on haemostasis – development of innovative biomedical antitrombotics.

Research activity

Code Science Field Subfield
3.06.00  Medical sciences  Cardiovascular system   

Code Science Field
P310  Natural sciences and mathematics  Proteins, enzymology 
B490  Biomedical sciences  Haematology, extracellular fluids 
B530  Biomedical sciences  Cardiovascular system 
Keywords
Vipera a. ammodytes, venom, haemostasis, anticoagulant phospholipase A2, fibrinolitic metalloproteinase, antitrombotics
Evaluation (rules)
source: COBISS
Researchers (6)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  25628  PhD Lidija Kovačič  Biochemistry and molecular biology  Junior researcher  2008 - 2009  82 
2.  00412  PhD Igor Križaj  Biochemistry and molecular biology  Head  2008 - 2011  736 
3.  18802  PhD Adrijana Leonardi  Biochemistry and molecular biology  Researcher  2008 - 2011  161 
4.  20213  PhD Toni Petan  Biochemistry and molecular biology  Researcher  2008 - 2011  179 
5.  04570  PhD Jože Pungerčar  Biochemistry and molecular biology  Researcher  2008 - 2011  320 
6.  30888  PhD Tamara Sajevic  Pharmacy  Junior researcher  2009 - 2011  24 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  91,836 
Abstract
Venomous animals represent a major source of highly selective and efficient bioactive compounds that have already led to the development of several innovative drugs. The proposed project is aimed at developing new drug candidates to prevent trombosis on the basis of anticoagulant phospholipase A2, ammodytoxin, and fibrinolytic metalloproteinase, ammodytase, from the venom of European most venomous snake Vipera ammodytes ammodytes. To achieve these goals, the complex between the blood coagulation factor Xa (FXa) and ammodytoxin will be structurally characterized. Based on the detailed structural information about the inhibition of FXa by ammodytoxin, short peptides or peptidomimetics with anticoagulant properties will be prepared. Ammodytase is a fibrinolytic metalloproteinase. As it is not toxic, it represents a promising substance to be used in clinics to dissolve blood clots. Ammodytase and its truncated forms will be prepared using protein engeneering and recombinant proteins thoroughly characterized for their biochemical and physiological properties. In addition, the repertoire of proteins from Vipera a. ammodytes venom will be systematically analysed for those components that interfere with haemostasis to discover new molecular tools to be used in blood testing and characterization.
Significance for science
According to World Health Organization (WHO), 29% of global deaths are caused by cardiovascular diseases, qualifying these kind of pathologies as one of the most critical for the mankind. Venous thromboembolic disease is also a major problem in the European Union, where it affects according to the 2007 data more than one million people every year. Moreover, WHO predicts that two leading causes of death in the world in 2030 will be ischemic heart disease and stroke (World Health Statistics 2008, WHO Statistical Information System – WHOSIS). Therefore, one of the strategic priorities of the WHO Cardiovascular Disease Programme (http://www.who.int/cardiovascular_diseases/priorities/en/) is to develop cost effective and equitable health care innovations for management of cardiovascular diseases to reduce morbidity and mortality caused by cardiovascular diseases. Anticoagulants are pivotal for the prevention and treatment of thromboembolic disorders which are one of the most severe medical problems nowadays in developed world indicated by the fact that nearly 1% of the western population receives anticoagulant treatment. It is expected that the problem will expand in the following years, as the population in these parts of the world is rapidly aging. For these reasons, intensive search for novel therapeutic approaches and substances in this medical area is highly relevant.
Significance for the country
The project was focused on analysis of the nose-horned venom machinery that affects the human haemostatic system in order to understand and exploit these findings for discovery of novel diagnostic and therapeutic procedures to cure human haemostatic dysfunctions. Numerous results that we obtained will have high and immediate impact on improvement of human health. Pharmacologically interesting results will enable further strengthening of our collaboration with especially domestic pharmaceutical industry. The concluded research project resulted in also several indirect positive impacts on our society. These are especially reflected in the education area. The research activities, first of all, aided to the scientific and professional growth of researchers and university teachers involved – some members of the project team are involved in teaching activities at undergraduate and postgraduate levels at different faculties. In the scope of the performed project students had been educated, a young researcher on her PhD study, as well as several undergraduate students working on their diplomas. Our knowledge and experiences had been thus directly transferred from the labs to the students. A part of the obtained results had been already published in six papers in high quality scientific journals, some are still under preparation. Together with dissemination of our achievements through lectures and postes on international scientific conferences, we extended the recognition and scientific reputation of Slovenia in the World. Of the special importance for the Slovenian research sphere and through it for the whole society is also introducing and transferring of the latest research technologies that we are use in our experimental work. In the scope of this project one of such state-of-the-art technology that was introduced and used was the proteomics.
Most important scientific results Annual report 2008, 2009, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, 2009, final report, complete report on dLib.si
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