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This volume is the first to combine latest information on viral,
microbial and cellular proteolytic enzymes as potential targets for
human therapeutics. Proteases control a large array of
physiological reactions, and are involved in a variety of
pathological processes for which effective medications are
currently needed and/or being sought after. Although protease
inhibitors have been investigated for many years, few have been
employed therapeutically. Recent break- through by HIV protease
inhibitors as therapeutic drugs has re-encouraged the search for
inhibitors of other proteolytic enzymes. Klaus von der Helm, who
described the first viral protease has brought leading experts
together to discuss not only the success and problems of clinical
use and continuing prospects, but to review further potential drug
targets. This volume provides detailed information and evaluations
of key viral, bacterial, fungal, and cellular proteases as
potential future drug candidates.
Proteolytic enzymes and their natural antagonists, the protease
inhibitor pro- teins, play a crucial role in the physiology and
pathology of living organisms including humans. Remark able
advantages revealed their wide functional context. Proteases digest
food proteinase in the digestive tract and liberate poly- peptide
hormones, stimulating gastric and pancreatic secretion. Proteases
are involved during fertilization in sperm - egg interaction,
ovulation, ovum implantation and parturition. Proteases of the
renin-angiotensin and kallikrein-kinin systems act synergistically
to generate blood pressure regu- lating polypeptides. In wound
healing a battery of proteases is involved in the proteolytic
cascades of clotting, fibrinolysis and tissue repair.Another
battery of very different proteases directs the immune defense via
several routes, i.e. complement activation, antigen presentation,
the generation of chemokines and chemotaxins directing phagocytes
to the site of injury or infection and the generation of
cell-stimulating factors such as cytokines regulating the inflam-
matory response of the organism.Granzymes contribute to the
toxicity of lym- phocytes or killer cells,caspases regulate
physiological cell death and calpains intracellular signaling
cascades. The energy-dependent proteasome-ubiquitin system controls
highly efficientl y the activity or level of intracellular
proteins, including cell-cycle regulators, transcription and signal
transduction factors, oncoproteins and short-lived metabolic
enzymes.And this listing is far from complete.
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