Collagenase and

Collagenases and hyaluronidases are produced by most of the aggressive invaders. These are able to dissolve eollagen fibres and hyaluronie aeids which function as intracellular cements. Their loss causes the tissues to breakup and produce oedematous lesions. 

The value of proteases in cleansing tissue wounds has been appreciated for several hundred years. Wounds were sometimes cleansed in the past by application of protease-containing maggot saliva. Nowadays, this is usually more acceptably achieved by topical application of the enzyme to the wound surface. In some cases, the enzyme is formulated in an aqueous-based cream, and in others it is impregnated into special bandages. Trypsin, papain, collagenase and various microbial enzymes have been used in this regard. 

Burger, D. et al., Imbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes Involvement of membrane-associated cytokines, Arthr. Rheum., 41, 1748, 1998. 

Inhibitors of human neutrophil collagenase and human stromelysin have been designed (577) which are based on previous classes of MMP inhibitors, iV-carboxyalkyl peptides (578, 579), and peptide-based hy-droxamic acids (117) (580, 581). The -CH3 and 2-phenylethyl groups are important for inhibition of MMP-3. The X-ray crystal structure of MMP-3 with bound 117 shows that the inhibitor chelates Zn(II)... 

Furthermore, the myeloperoxidase systems can stimulate secretion of serotonin from platelets, histamine release from mast cells and the activation of latent collagenase and latent gelatinase of neutrophils. 

Metalloproteases. The metalloproteases are so called because they require both calcium and zinc ions as cofactors. All known metalloproteases are secreted as inactive zymogens. The metalloproteases can be divided into three main groups (A4) interstitial collagenases, type IV collagenases, and the stro-melysins. 

KI3. Kossakouska, A. E., Urbanski, S. J., Huchcroft, S. A., and Edwards, R. R., Relationship between clinical aggressiveness of large cell immunoblastic lymphomas and expression of 92 kDa gelatinase (type IV collagenase) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Oncol. Res. 4, 233-240 (1992). 

Alpha-1 A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH]... 

Mammalian collagenases and the matrix metalloproteinases Collagenase assays Collagen-based assays Peptide-based assays... 

Stack and Gray have described a convenient, continuously recording, fluorescent assay for rabbit collagenase and gelatinase based on the hydroly-... 

Formation of incipient lesions. Specimens were exposed alternately to acid and collagenase (fig. 1). Erosive lesions were formed by demineralization in HAc (pH 5.0 and pH 5.5), subsurface lesions by demineralization in HLac-MHDP (pH 4.5 and pH 5.0). All specimens were incubated separately in 1.0 ml acidic solutions for six hours and 1.0 ml collagenase or buffer for 18 hours daily. Under these conditions, the amount of degradable organic matrix is proportional to mineral loss (Klont and Ten Cate, 1991). Between the incubations, the specimens were rinsed briefly with distilled water and dried with paper. Each acid/collagenase and acid/buffer group contained five specimens. The experimental period was ten days. All incubations were carried out at 37°C without stirring. 

Por fhe specimens of bafch III, bofh fhe collagenase and borohydride freafmenfs were omiffed fo enable analysis of furosine, which is formed by acid hydrolysis of fhe non-reduced glucose-lysine condensation producf. 

Hypersensitivity One case of systemic manifestations of hypersensitivity to collagenase occurred with treatment of more than 1 year with both collagenase and cortisone. 

The surface features of matrilysin, fibroblast collagenase, and neutrophil collagenase are all similar (Figure 4). The active-site groove can be plainly seen on the surface two main pockets punctuated by the active-site zinc. Modeling... 

Murphy G, Allan JA, Willenbrock, F, Cockett MI, Docherty AJP. The role of the C-terminal domain in collagenase and stromelysin specificity. J. Biol. Chem. 1992 267 9612-9618. 

Antinflammatory DMARDs such as chloroquine, auranofin, sodium aurothiomalate, and dexamethasone have been shown to inhibit IL-1 synthesis [89]. Analogs of these compounds have exhibited potent inhibition of IL-1 a- induced cartilage resorption [90]. Elevated collagenase and proteoglycanase levels caused by IL-1 in human cartilage were found to be reduced by tiapro-... 

Peptides with C-terminal phosphonates, initially reported to have antibacterial properties, have also been found to possess inhibitory properties toward serine proteases)28 The synthesis of peptide phosphonates (Section 15.1.8) usually requires protection of the phos-phonic moiety as a diester, followed by selective deprotection in the final stage. The importance of peptide thiols (Section 15.1.9) is exemplified by captopril, an orally active angiotensin converting enzyme inhibitor used as a treatment for hypertension)29 These peptide thiols are prepared by the reaction of sulfanylalkanoyl amino acids with a-amino esters followed by deprotection of carboxy and sulfanyl groups. Other peptide thiols have been reported to be inhibitors of zinc metalloproteases, collagenases, and aminopeptidases. 

Zinc proteases are metalloenzymes containing tightly bound zinc examples are carboxypeptidases A and B, collagenase, and thermolysin. The zinc atom is bound to the imidazole moiety of two histidines and the carboxylate of Glu the fourth ligand is a molecule of H20. 

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