Cardiovascular diseases (CVD) include a number of diseases of the heart and blood vessels, among which the leading one is coronary heart disease (CHD), leading to severe complications and deaths. Hypertension, often referred to as CVD, is one of the most common diseases and one of the leading causes of death worldwide. Arterial hypertension is a major risk factor for the development of CVD. Despite the existing progress, the search for effective treatment methods and the creation of drugs for the treatment of CVD remains a very urgent task. The fundamental scientific problem to be solved by the proposed project is the disclosure of the molecular mechanisms of protection of organs and tissues from damage under conditions of impaired blood supply. It has now been established that some peptides and proteins from animal venoms affect the functioning of the cardiovascular system (CVS). As a rule, animal toxins are characterized by high efficiency and selectivity of interaction with their biological targets. The scientific objective of the project is to study compounds derived from snake toxins that can reduce or prevent the negative effects of certain CVDs. Such compounds can be used in the future to develop new treatments for CVD. The goal of this project is to synthesize peptide fragments based on the structures of snake toxins and, using animal models, to determine their cardioprotective and hypotensive activity. These studies will make it possible to establish the structural elements responsible for the potent effects of the studied compounds on the functions of the cardiovascular system. The main objects of research are the components of snake venom, which in previous studies, including those carried out within the framework of the previous RSF project, showed the presence of activity in ex vivo and in vivo experiments. Thus, in particular, using the model of reperfusion injury, subunits of endothelial growth factor and synthetic peptide fragments of its amino acid sequence will be studied. Peptide fragments of the WTX toxin from cobra venom and heterodimeric phospholipases A2 from Nikolsky's viper will be studied as compounds that have a hypotensive effect. The activity of peptides synthesized based on these compounds will also be studied in vitro against nicotinic cholinergic receptors of different subtypes. The inotropic effects of the above compounds will be studied on the papillary muscle of the heart, and the vascular effects on the thoracic aortic rings. New peptide and protein compounds that can prevent or reduce the negative consequences of reperfusion syndrome and hypertension may further serve as the basis for the rational design of drugs to combat these diseases. Such a comprehensive study of the obtained original compounds using several in vitro, in vivo and ex vivo models will be carried out for the first time. The key to successfully completing this complex task is to combine the experience, skills and developments of laboratories from Moscow and Pushchino. Animal models developed and used by project participants from the Laboratory of Biological Testing of the Institute of Biochemical Chemistry will be used as the main model systems. The objects of the study will be compounds obtained from snake venom toxins, the synthesis, isolation and characterization of which are the strength of the project participants from the Laboratory of Molecular Toxinology of the Institute of Bioorganic Chemistry of the Russian Academy of Sciences. A relatively young team under the leadership of an experienced and actively cited toxicologist consists of specialists of sufficiently high qualifications to guarantee the receipt of the declared world-class results and the release of at least 9 publications indexed in the Web of Science and Scopus databases.