Collagenases properties

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

Due to the good nucleophilic nature of sulfur, formation of new C—S bonds is relatively easy. This property has been used for intramolecular peptide cyclization 1 and was exploited for preparation of methylenethio ether surrogates, t >[CH2—S], initially as peptide gap inhibitors for blocking collagenase action. 2 These surrogates were later converted into sulfoxide and sulfone derivatives. This expansion of amide replacements compelled a more generalized nomenclature system for pseudopeptides (amides with one or more amide bond surrogates) and led directly to the psi-bracket convention. 1 ... 

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. 

Ray S, Chattopadhyay N, Mitra A, Siddiqi M, Chatterjee A. 2003. Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin. J Environ Pathol Toxicol Oncol 22 49-58. 

The diffusion coefficient depends on a number of factors, including the molecular properties of solutes the structures of tissues, and temperature. The temperature-dependence is less critical for drug delivery, since the temperature in tumors is stable and close to the body temperature. The dependence of D on tissue structures is significant (Netti et al., 2000 Pluen et al., 2001). It is mediated through the size and the volume fraction of pores, the tortuosity of diffusion pathways, and the connectedness of pores (Yuan et al., 2001). Diffusion of macromolecules is faster in tissues with a lower collagen type I content (Pluen et al., 2001) or tissues treated with collagenase (Netti et al., 2000). However, there is no correlation between D and the concentration of total or sulfated glycosaminoglycans (Netti et al., 2000). 

There are several important technical questions to be addressed. Very useful would be a deterministic study to examine the effect of collagenase treatment on channel properties and calcium regulation in isolated adult fibers. In particular, dystrophin links the intracellular cytoskeleton to the extracellular matrix through the DAG, and provides mechanical support for the sarcolemma through this linkage. Thus, removal of the extracellular matrix with enzymes might be predicted to alter the consequence of loss of dystrophin. To address this, fibers could be mechanically isolated and pinned out, then treated with collagenase. 

Similarly, no crystal structure is available yet for the important class of Zn(II) enzymes that hydrolyze collagen. Collagenase has some very unusual properties, being activated by organomercurials, and Mallya and Van Wart have reported a remarkable inhibition of human neutrophil collagenase by the antiarthritic drugs aurothiomalate and aurothioglucose at nanomolar concentrations (138). The activity of such enzymes in vivo may be finely controlled by local concentrations of Zn(II), Cu(I), and inhibitors such as Au(I). 

C. perfringens is the most important of the histotoxic clostridia that cause tissue infections in humans, especially of the muscle tissue (clostridial myonecrosis or gas gangrene). The organism is more aerotolerant than most other anerobes. In addition to toxins and enzymes, many of which have lethal, cell-destroying and hemolytic properties, a number of nonlethal enzymes are also produced and apparently contribute to the invasiveness of the organism in the tissue. These include collagenase, deoxyribonuclease, and hyaluronidase. 

The biochemical properties of chloroquine and related anti-malarials have been exeonined further. In addition to its inhibition of the biosynthesis of sulfated mucopolysaccharides, chloroquine inhibits irreversibly an autolytic enzyme from bovine cartilage and a rat skin collagenase (at 10 mM). Like hydrocortisone, it inhibits chemotaocis of leukocytes and, to a lesser extent, the phagocytosis process.It also stabilizes lysosomal membranes in vitro. Potential "anti-degenerative" activity is clearly suggested by these properties, but unfortunately the well-known retinopathic effect is further complicated by a delayed symptom. 

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