Current Pharmaceutical Design - Volume 13, Issue 3, 2007

Proteases have been known for many years as protein-degrading enzymes. However, this view has dramatically changed and proteases are now considered as extremely important signalling molecules, involved in numerous vital processes. Their activity requires strict regulation and regulation defects can lead to pathologies, often associated with excessive proteolysis. The number of diseases, where proteases were i Read More

Recent advances in global genomic and proteomic methods have lead to a greater understanding of how genes and proteins function in complex networks within a cell. One of the major limitations in these methodologies is their inability to provide information on the dynamic, post-translational regulation of enzymatic proteins. In particular proteases are often synthesized as inactive zymogens that need to be activated in order t Read More

We illustrate the use of quantitative proteomics, namely isotope-coded affinity tag labelling and tandem mass spectrometry, to assess the targets and effects of the blockade of matrix metalloproteinases by an inhibitor drug in a breast cancer cell culture system. Treatment of MT1-MMP-transfected MDA-MB-231 cells with AG3340 (Prinomastat) directly affected the processing a multitude of matrix metalloproteinase subst Read More

Aspartic proteases are the smallest class of human proteases with only 15 members. Over the past years, they have received considerable attention as potential targets for pharmaceutical intervention since many have been shown to play important roles in physiological and pathological processes. Despite numerous efforts, however, the only inhibitors for aspartic proteases currently on the market are directed against th Read More

The drawbacks and limitations of existing anticoagulant therapy which may result in serious adverse effects and a high mortality rate, have given rise to many anticoagulant development programmes in the last decade, focusing mainly at development of thrombin and FXa low-molecular weight inhibitors. A detailed understanding of blood coagulation pathways, functioning of the serine proteases thrombin, FXa, FVIIa and Read More

Tryptases comprise a group of trypsin-like serine proteases that are highly and selectively expressed in mast cells and to a lesser extent in basophils. Among them interest has been focused on tryptase β, primarily because it was the first tryptase identified and because it is the predominant protease and protein component of mast cells. Subsequent studies have provided convincing evidence that tryptase β is n Read More

The matrix metalloproteinase family of enzymes has been a pharmaceutical target for over 20 years. In that time, many drugs have been developed but none have successfully passed clinical trials. A significant problem has been development of dose-limiting side-effects that were revealed during long-term clinical trials in diseases such as arthritis and various cancers. There are, however, other clinical settings whe Read More

Metallocarboxypeptidases (MCPs) are commonly regarded as exopeptidases that actively participate in the digestion of proteins and peptides. In the recent years, however, novel MCPs comprising a wide range of physiological roles have been found in different mammalian extra-pancreatic tissues and fluids. Among them, CPU, also known as thrombinactivatable fibrinolysis inhibitor (TAFI), has been shown to cleave C-termina Read More

This review provides an overview of the biochemistry and activation of inflammatory caspases, and focuses on their therapeutic potential as disease targets in pathologies such as sepsis, Crohn´s disease, rheumatoid arthritis, traumatic brain injury and amyotrophic lateral sclerosis (ALS). We summarize the proof-of-principal evidence obtained by studies in several corresponding experimental disease models confirming the Read More

The general view on cysteine cathepsins, which were long believed to be primarily involved in intracellular protein turnover, has dramatically changed in last 10 to 15 years. The discovery of new cathepsins, such as cathepsins K, V, X, F and O, and their tissue distribution suggested that at least some of them are involved in very specific cellular processes. Moreover, gene ablation experiments revealed that cathepsins play Read More

Influenza A virus (IAV) is one of the most common infectious pathogens in humans. Since IVA genome does not have the processing protease for the viral membrane fusion glycoprotein precursors, entry of this virus into cells is determined primarily by host cellular, trypsin-type, processing proteases that proteolytically activate the fusion glycoprotein precursors of IAV. At least five different processing proteases have been id Read More