Alfa 1-Proteinase inhibitor (Human)

Metalloprotease inhibitorsare cellularinhibitorsof thematrix metalloproteinases(MMPs).MMPs belong to a family ofzinc-dependent neutralendopeptidases.Theseenzymeshave the ability to break downconnective tissue. The expression of MMPs is increased in variouspathologicalconditions likeinflammatoryconditions, metabolic bone disease, tocancerinvasion,metastasisandangiogenesis. Examples of diseases areperiodontitis,hepatitis,glomerulonephritis,atherosclerosis,emphysema,asthma, autoimmune disorders of skin and dermal photoaging,rheumatoid arthritis,osteoarthritis,multiple sclerosis,Alzheimer's disease, chronic ulcerations, uterine involution,corneal epithelial defects, bone resorption and tumor progression and metastasis.Due to the role of MMPs in pathological conditions, inhibitors of MMPs may have therapeutic potential.Several other proteins have similar inhibitory effects, however none as effective (netrins, procollagen C-terminal proteinase enhancer (PCPE), reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and tissue factor pathway inhibitor (TFPI-2)). They might have other biological activities which have yet been fully characterised. MMP inhibitors can broadly be subdivided into non-synthetic (e.g.endogenous) orsynthetic.Several potent MMP inhibitors have been identified, including hydroxymates,thiols,carbamoylphosphonates,hydroxyureas,hydrazines,β-lactams,squaric acidsand nitrogenous ligands. There are three classes of commonly usedinhibitorsformetalloproteinases. In vitro,EDTA,1,10-phenanthrolineand otherchelating compoundslower the concentration of metal to the point where the metal is removed from theenzymeactive site.Classical lock and key inhibitors such asphosphoramidonandbestatinbind tightly by approximating thetransition stateof the hydrolysis of the peptide, preventing it from acting on other substrates.Protein inhibitors such as α2-macroglobulinare known to work with metalloproteinases.