Rendezvény
Ivan Bogdanov előadása a Bioanalitika Intézetben
2023. jún. 14. | 10:00–11:30
Institute of Bioanalysis, Library / Faculty of Medicine (Pécs, Honvéd utca 1.)
June 14, 2023 / 10:00 a.m.
Institute of Bioanalysis, Library / Faculty of Medicine (Pécs, Honvéd utca 1.)
Title: "Structural and mechanistic insights into the advances of FXIIIa inhibitors"
Ivan Bogdanov,
PhD student, Institute of Molecular Biology, Bulgarian Academy of Sciences
Abstract
In this study, we present an innovative platform for structure-based drug design and screening rely on single crystal X-ray diffraction and molecular docking using SeeSAR tool (SCXRD/SeeSAR) in order to analyse the interaction between FXIIIa and novel ligands. As a result, the binding affinities (including their physicochemical and drug-like properties) of selected small-molecular-based compounds using the embedded in SeeSAR “HYDE” (HYdrogen DEsolvation) algorithm were estimated. In addition, SAR of the different types of analysed (small molecules and peptidomimetics) FXIIIa inhibitors is shown. FXIIIa is a promising alternative target for development of novel anticoagulants for the therapy of thrombosis."
Background: Cardiovascular diseases (CVDs) represent a major problem to humanity, having the highest mortality rates (above 85% of the deaths caused are due to heart attacks and strokes) in the category of natural causes according to the WHO. A way of dealing with this problem is the fast treatment with anticoagulants inhibiting the activity of blood clotting factors and further causing an impact on the process of thrombosis by altering and stopping the clot formation. As a result, they protect the patients from fatal consequences. Inhibitors targeting blood clotting factor XIIIa (FXIIIa), involved in the last step of coagulation process, have been considered to develop a new generation of anticoagulants. Plasma FXIIIa is an enzyme, belonging to the family of transglutaminases, that is primary responsible for stabilization of the fibrin network by stabilizing the preformed clot. Normally, found in the blood plasma, FXIII is comprised of two dimeric-catalytic FXIII-A and two dimeric-regulatory FXIII-B subunits. After vascular injury the FXIII-A subunit is cleaved by thrombin and together with Ca2+-binding is activated to its active form - FXIIIa.