can any one suggest list of protease inhibitors list & if possible reference - (Aug/23/2006 )

can any one suggest list of protease inhibitors list & if possible references[u]
I am working on thermophilic protease from bacteria & fungi.
I am doing project in microbiology as I am student in microbiology( HM with biotechnology & biochemistry )

Find the Sigma catalogue.

Look up Protease Inhibitors and all will be explained.

hi go through this link from science gate way

Resources: Protease Inhibitors
The following table gives an overview on the use and application of frequently used protease inhibitors in biochemistry and cell biology. It summarizes information on the mechanism of action, target protease class, solubility, concentration, and lists corresponding references.

Protease Inhibitors
1M.W.
2 Description/Specificity of Inhibitor
3Solubility
4Stability
5Concentration
6Range a)
References

AEBSF-HCl
239.7
Irreversible inhibitor of Thrombin and other serine proteases. Inhibits by acylation of the active site of the enzyme. Much less toxic than PMSF and DFP
H2O, Aqueous solutions are stable between pH 5-6
0.1 - 2mM
60,83,84

Amastatin-HCl
511
Non-toxic reversible metallo-protease inhibitor. Inhibits many membrane-bound peptidases which are critical regulators of peptide hormones, e.g. aminopeptidase A and M, but not aminopeptidase B. Inhibits also leucine aminopeptidase.
Ethanol
0.5 % AcOH
1 - 100 µM
1,2,3,4

(epsilon)-Aminocaproic acid
131.2
Highly active inhibitor of fibrinolysin and chymotrypsin.
H2O
1 - 20 mM
5,6

(alpha)1-Antichymotypsin from human plasma
68000
Glycoprotein that inhibits chymotrypsin-like proteases (above all human neutrophil cathepsin G) by forming stable complexes. Acute phase protein; concentration in plasma increases after events like inflammation or tissue damage
Aqueous buffers
Used at equimolar concentration
7,8,9,10

Antipain-HCL
678.2
Reversible inhibitor of serine and cysteine proteases. Inhibits papain and trypsin more specificity than leupeptin. Plasmin is inhibited only slightly. Also involved in inhibition of RNA synthesis
H2O
Methanol DMSO
1 - 100 µM
11,12,13

Antithrombin III from human plasma
ca. 60000
Glycoprotein that plays a major role in controlling serine proteases in the blood clotting cascade. Inactivates above all thrombin by forming an extremely stable complex, an effect which is enhanced by heparin. Inhibits also other proteases of the coagulation cascade like plasmin, kallikrein, factor IXa, Xa, XIa and XIIa.
H2O
Used at equimolar concentrations
8,14 15,16

(alpha)1-Antitrypsin from human plasma ((alpha)1-proteinase inhibitor)
ca. 53000
Glycoprotein that is mainly involved in the control of neutrophil elastase activity. Inhibits also most of other mammalian serine proteases but at a lower rate. Blocks the action of target enzymes by binding nearly irreversibly to their active site.
H2O
Aqueous buffers


Used at equimolar concentrations
8,9,17,18,19

APMSF-HCl
(4-Amidinophenyl-methane
sulfonyl-fluoride)
252.7
Irreversible inhibitor of trypsin-like serine proteases. Stronger inhibitor than PMSF, but does not inhibit chymotrypsin and acetylcholine esterase.
H2O
(20 mg/ml).
Aqueous solutions are stable when stored in aliquots at -20 °C
10-50 µM
20,21

Aprotinin (Trypsin inhibitor from bovine lung)
ca. 6500
Basic single-chain polypeptide that inhibits numerous serine proteases by binding to the active site of the enzyme, forming tight complexes. It inhibits above all plasmin, kallikrein, trypsin, chymotrypsin and urokinase, but not carboxypeptidase A and B, papain, pepsin, subtilisin, thrombin and factor X. Used in cell culture to prevent proteolytic damage to cells and to extend lifetime of cells.
H2O, Aqueous buffers. Sterile filtered solutions at pH 5-8 are stable for several months. Denatures at pH > 12
In cell culture: 0.01 - 3 µg/ml; in other applications: 10 - 250 µg/ml
22,23,24,25

Arphamenine A
387.4
Inhibitor of the metallo-protease Aminopeptidase B
H2O, MeOH
IC50:
0.006 µg/ml
85,86

Arphamenine B
403.4
Inhibitor of the metallo-protease Aminopeptidase B
H2O, MeOH
IC50:
0.002 µg/ml
85,86

Benzamidine-HCl
174.6
Potent inhibitor of thrombin and trypsin
H2O
0.1 - 50 mM
26,27,28

Bestatin-HCl
344.8
Metalloprotease inhibitor with multi-pharmacological functions. Inhibits cell surface aminopeptidases (notably and leucine aminopeptidase. Inhibitor of leukotriene A4 hydrolase and of enkephalin degradation in cell preparations from brain. Has anticarcinogenic and immunomodulating properties.
Methanol
(5 mg/ml)
1 - 150 µM
Mitogenic effects at nmolar concentrations
29,30,31,32,33

CA-074
383.4
Inhibitor of Cathepsin B
DMSO
0.01 - 1 µM
87,88,89

CA-074-Me
397.5
Proinhibitor for intracellular Cathepsin B. Membrane-permeable analog of CA-074
DMSO
1 µM
90

Calpain Inhibitor I
367.2
Tripeptide aldehyde. Specific inhibitor of the Ca2+-dependent cysteine protease calpain I and of cathepsin B and L.
Ethanol,
Methanol, DMF, DMSO (10 mg/ml)
1 - 50 µM
34,35,36

Calpain Inhibitor II
385.2
Tripeptide aldehyde. Specific inhibitor of the Ca2+-dependent cysteine protease calpain II and of cathepsin B and L.
Ethanol, Methanol, DMF, DMSO
(10 mg/ml)
1 -50 µM
35,36,37,38

Cathepsin Inhibitor Z-Phe-Gly-NHO- Bz-pMe
489.5
Specific inhibitor of Cathepsin B/L/S and Papain
DMSO, EtOH, Acetonitrile
Ki:
0.15 - 16 µM
91,92

Chymostatin
ca. 600
Peptide-derived aldehyde (mixture of 3 components). Reversible inhibitor of chymotrypsin-like serine and some cysteine proteases
DMSO
Acetic acid
10 - 100 µM
11,39,40,41

DFP
(Diisopropylfluoro-phosphate)
184.2
A potent irreversible inhibitor of serine proteases and acetyl choline esterase. Highly toxic!
Isopropanol; aqueous solutions are unstable
10 - 100 µM
28,42,43

Dipeptidylpeptidase IV Inhibitor
H-Glu-(NHO-Bz)Pyr
354.8
Reversible inhibitor of Dipeptidylpeptidase IV/CD26 and Prolylendopeptidase
DMSO, EtOH, H2O
Ki:
1 µM
93

Diprotin A
341.5
Reversible inhibitor of the metallo-protease Dipeptidylaminopeptidase IV
H2O
Ki:2.2 µM
94

E-64
357.4
Non-competitive irreversible inhibitor of papain and other cysteine proteases. Forms a thioether bond with the sulfhydryl group in the active center of the enzyme. Useful for active site titration: one mole of E-64 inhibits one mole of protease.
H2O, DMSO Mixtures of water and ethanol
1 - 10 µM
51,52,53

E-64d (EST)
342.4
Membrane-permeable analog of E-64c
DMSO
1 µM
90,99,100

Ebelactone A
338.5
Non-toxic inhibitor for esterases, acylpeptide hydrolase, lipase and N-formylmethionine aminopeptidase
Methanol (200 mg/ml)
1 - 10 µM
43,44,45

Ebelactone B
352.5
Non-toxic inhibitor for esterase, lipase and N-formyl-methionine aminopeptidase. Inhibits also carboxypeptidase Y-like exopeptidase.
Methanol (200 mg/ml)
1 - 10 µM
44,46,47

EDTA-Na2
372.3
Reversible inhibitor of metalloproteases
H2O (pH 8)
1 - 10 mM
48,49

EGTA
380.4
Inhibits metalloproteases.. Reveals high selectivity for Ca2+ over Mg2+ ions.
NH4OH, NaOH
1 - 10 mM
50

Elastatinal
512.6
Inhibitor of Elastase
H2O, MeOH, DMSO
Ki: 0.21 µM
(with Ac-Ala-Ala-Ala-OMe as substrate)
11

Hirudin
7027
Inhibits thrombin by blocking substrate binding groups
H2O
Aqueous buffers
Used at equimolar concentrations
54,55

Leuhistin
241.3
Inhibitor of Aminopeptidase M
H2O, DMSO,
EtOH, MeOH
IC50:
0.2 µg/ml
102,103,104

Leupeptin-
hemisulfate
475.6
Tripeptide aldehyde. Reversible competitive inhibitor of serine and cysteine proteases. Inhibits also phospholipase D and C activation in rat hepatocytes.
H2O
Stable for sereval months when stored in aliquots at -20 °C
1 - 100 µM
11,56,57,58

(alpha)2-Macroglobulin from human plasma
725000
Glycoprotein composed of 4 identical subunits. Broad-range endoproteinase inhibitor. Inhibits by forming a »trap« around the enzyme allowing only small substrate molecules to enter and to be cleaved by the entrapped protease.
H2O
Stable for several months when stored in aliquots at -20 °C
Used at equimolar concentrations
8,59

PEFABLOC® SC </SUP< sup>
4-(2-Aminoethyl)-benzenesulfonyl fluoride hydrochloride
239.5
Water-soluble and relatively non-toxic irreversible inhibitor of thrombin and other serine proteases. Inhibits by acylation of the active site of the enzyme.
H2O
(20 g/100 ml) Stable for several months between pH 5 - 6; limited stability above pH 7.5
0.1 - 5 mM in cell culture: 0.1 - 0.25 mM
60,61,62

Pepstatin A
685.9
Pentapeptide derivative. Reversible inhibitor of aspartic proteases, e.g. pepsin, cathepsin D, chymosin, renin
Methanol
(1 mg/ml) DMSO
1 - 10 µM
11,63,64,65

Phebestin
441.5
Inhibitor of Aminopeptidase N
H2O, DMSO, MeOH
IC50:
0.18 µg/ml
105

PMSF
Phenylmethyl sulfonyl fluoride
174.2
Irreversibly inhibits serine proteases by sulfonylation of the serine residue in the active site of the protease. Inhibits also papain (reversible by DTT treatment) and acetylcholin-esterase. Does not inhibit metallo-, aspartic- and most cysteine proteases.
Isopropanol, ethanol, methanol. (100 - 200mM) Unstable in aqueous solution
0.1 - 1 mM
66,67,68

Phosphoramidon
587.5
Specific inhibitor of thermolysin and neutral endopeptidase-24.11 (ANP Degradation Enzyme). Inhibits also the activity of Endothelin Converting Enzyme, collagenase and metallo-endoproteinases from many microorganisms. Does not inhibit serine, cysteine and aspartic proteases
H2O
(20 mg/ml) DMSO Methanol
1 - 100 µM
11,69,70,71,72

TLCK
(1-Chloro-3-tosylamido-7-amino-2-heptanone HCl)
369.3
Irreversibly inhibits trypsin but not chymotrypsin by alkylating the histidine residue in the active site of the enzyme. Inhibits also some other serine and cysteine proteases like bromelain, ficin and papain. TLCK does not react with zymogens or in active protease-inhibitor complexes.
1 mM HCl, DMSO H2O
(20 mg/ml). Aqueous solutions are unstable above pH 7
10 - 1000 µM
73,74,75,76

TPCK
(1-Chloro-3-tosylamido-4-phenyl-2-butanone)
351.8
Irreversibly inhibits chymotrypsin but not trypsin by specifically reacting with histidine. Inhibits also other serine and cysteine protease such as bromelain, ficin and papain.
Ethanol (20 mg/ml) sparingly soluble in water; unstable at alkaline pH
10 - 1000 µM
62,77

Trypsin inhibitor from egg white
(Ovomucoid)
ca. 28000
Monomeric Glycoprotein. Inhibits bovine (but not human) trypsin in a 1:1 molar ratio. Inhibition is reversible and pH dependant.
H2O, 1 mM HCl
(1 mg/ml) Very stable between pH 3 - 7 against heat and 9 M urea. Unstable at alkaline pH
Used at equimolar concentrations
(10-100 µg/ml)
78,79,80

Trypsin inhibitor from soybean
ca. 22000
Monomeric protein. Reversible serine protease inhibitor. Inhibits trypsin, factor Xa, plasmin and plasma kallikrein, but not tissue kallikrein.
H2O
(1 mg/ml) Sensitive to heat and high pH
Used at equimolar concentrations (10-100 µg/ml)
81,82

a) Concentration range refers to data frequently used in the literature. The optimal concentration depends very much on the test system under investigation and has to be determined in each case empirically.
PEFABLOC is a registered trademark of Pentapharm/Basel

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