Development of biologicaly active peptidomimetics

Biologically active inhibitors of thrombin will be developed. Thrombin is the key serine proteinase of the coagulation cascade and therefore a suitable target for the inhibition of blood coagulation. In the present project peptidomimetics will be designed and synthetised according to the medicinal chemistry principles. In order to obtain new lead compounds, plant and fungi extracts will be prepared as well and tested in vitro. Active fractions will be isolated and their structure determined by different scpectroscopic methods. The isolated compounds - lead compounds- will serve as a new starting-point for the development of (peptido)mimetics with antithrombotic activity. Basic properties of the newly synthsized compounds will be determind, using different physical and chemical methods. The potential therapeutic value of the new compounds will be estimated on the basis of various enzyme and coagulation tests; the inhibitory activity of the products on thrombin and trypsin will be determined spectrophotometrically, using an appropriate chromogenic substrat. For the most promising compounds the basic toxicity studies will be performed. The project also includes pre-formulation studies which should contribute to a more reliable evaluation of biological effects and to the optimization of the synthesis of new potential drugs.