Current Pharmaceutical Design - Volume 8, Issue 18, 2002

Cysteine proteases are widespread in nature. Their implication in numerous vital processes and pathologies make them highly attractive targets for drug design. The proper functioning and regulation of activity of cysteine proteases is a delicate balance of many factors, one of the most crucial being the protease inhibitors. In this review the basic principles of physiological protease inhibition by protein inhibitors are discussed wit Read More

Thirteen papain-like cysteine proteases (cathepsins) are coded in the human genome from which two represent pseudogenes. Initially it was believed that lysosomal cysteine proteases primarily fulfill house-keeping functions which would exclude them as potential drug targets. Within the last decade, this view has dramatically changed and highly specific and therapeutically relevant functions have been assigned to individu Read More

New drugs to treat malaria are urgently needed. Cysteine proteases of malaria parasites offer potential new chemotherapeutic targets. Cysteine protease inhibitors block parasite hemoglobin hydrolysis and development, indicating that cysteine proteases play a key role in hemoglobin degradation, a necessary function of erythrocytic trophozoites. These inhibitors also block the rupture of erythrocytes by mature parasit Read More

The application of various molecular modeling techniques has been recently reported in the design of several new cysteine protease inhibitors. Computational chemistry techniques have been used to understand and predict enzyme-inhibitor interactions and also to study enzyme mechanism and inhibitor reactivity. This review focuses on examples that use structure-based design or reflect cysteine proteases as a target class. Read More