As serine protease

Coagulation Factors II, III, VII, IX, X, XI, and Xlla fragments, thrombin, and plasmin are classified as serine proteases because each possesses a serine residue with neighboring histidine and asparagine residues at its enzymatically active site (Table 3). Factors II, VII, IX, and X, Protein C, Protein S, and Protein Z are dependent on the presence of vitamin K [84-80-0] for their formation as biologically functionally active procoagulant glycoproteins. 

More than 50 endogenous and exogenous inhibitors of the calpains have been described as either transition-state reversible or irreversible inhibitors. The first transition-state inhibitors were the peptide aldehydes (e.g., leupeptin). Using this compound, new ones were synthesized that exhibited improved membrane permeability and calpain specificity (e.g., calpeptin). Other groups of inhibitors have since been discovered a-dicarbonyls (originally developed as serine protease inhibitors), nonpeptide quinolinecarboxamides,... 

Pochet, L., Frederick, R. and Masereel, B. (2004). Coumarin and isocou-marin as serine protease inhibitors. Curr. Pharm. Des. 10, 3781-3796. 

The catalytic mechanism of the subtilisins is the same as that of the digestive enzymes trypsin and chymotrypsin as well as that of enzymes in the blood clotting cascade, reproduction and other mammalian enzymes. The enzymes are known as serine proteases due to the serine residue which is crucial for catalysis (Kraut, 1977 and Polgar, 1987)... 

Coupling of the isothiazolo[5,4- ]pyridine 114 with compound 115 affords useful compounds as serine protease inhibitors (Equation 25) <2003JME4428>. 

Most peptidyl a,a-difluoroalkyl ketones are actually extended chains based on statone, rather than simple difluoromethyl ketones. The statone derivatives are based on pepstatin, which is an extremely potent peptide inhibitor of aspartic proteases. The difluoro derivatives of statone take advantage of both the electronegativity of fluorine and the potential for additional interactions between the protease and structures on the leaving group side of the inhibitor. 15 This dual nature is part of what makes a,a-difluoroalkyl ketones effective inhibitors of aspartyl proteases as well as serine proteases. There are three main methods of synthesizing peptidyl a,a-difluoroalkyl ketones (1) the Reformatsky reaction with peptide aldehydes (Section 15.1.4.2.1), (2) a modified Dakin-West reaction (Section 15.1.4.2.2), and (3) a Henry nitro-aldol condensation (Section 15.1.4.2.3). 

It adds (equation 17) to a-amino acid derived oxazolidin-5-ones giving, after acid hydrolysis, protected a-amino trifluoromethyl ketones80, which are of interest as serine protease inhibitors. 

Phosphonates and phosphonamidates were selected as transition-state analogs for carbonate and ester hydrolysis they are relatively stable molecules, they are known inhibitors of acyl transfer enzymes and they imitate the initial negative charge of the tetrahedral oxyanion of acyl transfer enzymes (such as serine proteases) in the dipole of the P=0 bond. 

Protease inhibitors aprotinin or/and PMSF as serine protease inhibitor. 

In earlier, (I), and subsequent investigations, (II), by the authors (1,2), respectively, additional pyrimidinone derivatives were prepared, which were effective as serine protease inhibitors, and used in the treatment of thrombotic disorders. 

Most of the fectors involved in blood coagulation and fibrinolysis systems are proteolytic enzymes. They are members of a class of catalysis known as serine proteases and share a common basic mechanism of action. These... 

Trypsin, chymotrypsin, and elastase are members of a large group of endopeptidases known collechvely as serine proteases. Recall that an endopephdase cleaves a pephde bond that is not at the end of a peptide chain (Sechon 23.12). They are called proteases because they catalyze the hydrolysis of protein pephde bonds. They are called serine proteases because they all have a serine residue at the achve site that parhcipates in the catalysis. 

The utilization of an active site serine to cleave a peptide bond is common to a variety of enzymes referred to as serine proteases. Serine proteases are essential for activating the formation of a blood clot from fibrin. Fibrin and many of the other proteins involved in blood coagulation are present in the blood as inactive precursors or zymogens, which must be activated by proteolytic cleavage. Thrombin, the serine protease that converts fibrinogen to fibrin, has the same aspartate-histidine-serine catalytic triad found in chymotrypsin and trypsin. 

The serine residue at position 195 is required for the activity of chymotrypsin in this respect, chymotrypsin is typical of a class of enzymes known as serine proteases. Trypsin and thrombin, mentioned previously, are also serine proteases (see the Biochemical Connections box on page 193). The enzyme is completely inactivated when this serine reacts with diisopropylphosphofluori-date (DIPF), forming a covalent bond that links the serine side chain with DIPF. The formation of covalently modified versions of specific side chains on proteins is called labeling it is widely used in laboratory studies. The other serine residues of chymotrypsin are far less reactive and are not labeled by DIPF (Figure 7.12). 

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