Development of Inhibitors of against Human Peroxidases

The currant project concerns development of pharmaceuticals which works as inhibitors against human peroxidases particularly: Myeloperoxidase (MPO), Eosinophile Peroxidase (EPO) and Laktoperoxidase (LPO). Besides, use of inhibitors in analytical kits to measure and investigate activities and properties of peroxidases should be considered.

Human peroxidases are haeme proteins and most abundantly present in subtypes of white blood cells: MPO in neutrophile granulocytes, EPO in eosinophile granulocytes. They are used by the immune defense to kill bacteria and pathogens by oxidising biomolecules and therefore inactivating and blocking microorganisms.

However, local overproduction of MPO and EPO leads to inflammation and tissue damage responsible for several diseases as artherosclerosis, respiratory tract diseases like COPD (chronic obstructive pulmonary disease), CNS-diseases, asthma and so on. Development of therapeutic intervention strategies aiming at efficient MPO and EPO inhibition is the long-term objective of the project.

Aim of this project is a systematic design of inhibitors against aggressive peroxidases MPO, LPO and EPO by data processing and computer applications. Our approach is the use of databases including natural material in combination with molecular modelling. By programming a mathematical algorithm and by definition of specific pharmacophores which resembles the typical peroxidase inhibitor expanded search of natural substance databases is possible. Results of the database screening should be presumable inhibitors which are tested and verified on enzyme activity.