Protease inhibitors trypsin

Arabidopsis tlialiana (mouse-ear cress) (Brassicaceae) Arabidopsis genes encoding - 8 kDa Potato type 1 serine protease inhibitors Trypsin (inferred) [438]... 

Phenylmethanesulfonyl fluoride (PMSF) [329-98-6] M 174.2, m 90-91 , 92-93 . Purified by recrystn from ""CgHe, pet ether or CHCl3-pet ether. [Davies and Dick J Chem Soc 483 1932 cf Tullock and Coffman J Org Chem 23 2016 I 960.] It is a general protease inhibitor (specific for trypsin and chymotrypsin) and is a good substitute for diisopropylphosphoro floridate [Fahrney and Gould 7 Am Chem Soc 85 997 1963]. 

There is evidence that protease inhibitors selectively regulate the activity of specific digestive enzymes at the level of gene expression (Rosewicz et al., 1989). Specifically, soybean trypsin inhibitor increases secretion of proteases, including a form of trypsin that is resistant to inhibition but does not cause an increase in amylase secretion. Although the relationships between protease inhibitors and exocrine pancreatic secretion have received the most attention, pancreatic secretion is increased when potato fiber is added to the diet (Jacob et al., 2000), although the mechanism and signaling pathway have not been elucidated. 

Our initial parametrization of the LIE equation was subsequently used for HIV protease and trypsin inhibitors as well as in a study of sugar binding to a bacterial receptor protein. While it was at first suspected that a... 

Hexokinase Pyruvate kinase Adenylate kinase Phosphoglycerate kinase Phosphofructokinase Protease inhibitors Pancreatic trypsin inhibitor Soybean trypsin inhibitor Streptomyces subtilisin inhibitor Nucleases... 

Serine protease inhibitor that inhibits trypsin, chymotrypsin, kallikrein, and plasmin Binding is reversible, with most aprotinin-protease complexes dissociating at pH>10or <3 Peptidase inhibitor... 

Inhibitor of serine and cysteine proteases plasmin, trypsin, papain and cathepsin B Inhibitor of type 1 and type 2A protein phosphatases... 

Potll inhibitors inhibit several proteases. For example, serine protease inhibitors isolated from Capsicum annum seeds named PSI-1.1 and PST1.2 are strong inhibitors of trypsin and only one order of magnitude less active on chymotrypsin. PSTl.l also has considerable activity against thrombin, whereas factor Xa is inhibited to a lesser extent by PSI-1.1 and PSTl.2. ... 

This approach was first applied toward an understanding of discriminating interactions in the serine proteases factor Xa, thrombin and trypsin [108] and provided selectivity information for all important serine protease subpockets, which are in agreement to experimental selectivities of typical protease inhibitors. This approach was complemented by a 3-D-QSAR selectivity analysis on a series of 3-amidinobenzyl-lH-indole-2-carboxamides [107], which points, from the viewpoint of the ligands, to similar main interactions driving selectivity between key enzymes in the blood... 

Total protein, albumin, urea (standard methods) and middle molecules (MM) were determined in citrated plasma [6]. The trypsin-like activity (TLA) of plasma was measured using the chromogenic peptide substrate (Z-glycyl-glycyl-L-arginine-4-nitroanilide) [7]. Evaluation of anti-enzymatic potential in plasma was based on concentrations of the main protease inhibitors -proteinase inhibitor (ttj-PI) and aj-macroglobulin (a -M). Student s t-test was used for statistical analysis. 

The clinical effect of Ovosorb can be attribnted to its effect on rednction of proteolytic activity in plasma and, as a resnlt, restoration of the balance between proteases and their inhibitors. Immediately after hemoperfnsion, in spite of decrease of the trypsin-like activity, the activity of protease inhibitors in plasma remained at its initial low level. This fact is in line with onr knowledge on the rates of biosynthesis of these proteins. 

About 20 families of protein inhibitors of proteases have been described.488 The egg white ovomucoids comprise one family. Turkey ovomucoid is a three-domain protein whose 56-residue third domain is a potent inhibitor of most serine proteases.455 489 The 58-residue pancreatic trypsin inhibitor490 is a member of another family of small proteins. A 36-residue insect (locust) protease inhibitor is even smaller.491... 

Several inhibitor-protease complexes have been crystallized and details of their interactions are known. For example, the pancreatic trypsin inhibitor binds at the active site of trypsin with K( >1013 M-1 at neutral pH 496 Tire two molecules fit snugly together,490 497 the inhibitor being bound as if it were a peptide substrate with one edge of the inhibitor molecule forming an antiparallel (1 structure with a peptide chain in the enzyme. Lysine 15, which forms part of this P structure, enters the specific Pj binding site for a basic amino acid in a substrate. Thus, the protease inhibitor is a modified substrate which may actually undergo attack at the active site. However, the fit between the two... 

Most protease inhibitors act by mechanisms similar to that of the pancreatic trypsin inhibitor. They are very slow substrates with a reactive loop that carries suitable Pj, P2, and P/ residues that meet the specificity requirements of the enzyme. Additional noncovalent interactions prevent dissociation and make the energy barrier for hydrolysis so high that the reaction is extremely slow.488 494 495... 

As mentioned above, the rectal route is very attractive for systemic delivery of peptide and protein drugs, but rectal administration of peptides often results in very low bioavailability due to not only poor membrane penetration characteristics (transport barrier) but also due to hydrolysis of peptides by digestive enzymes of the GI tract (enzymatic barrier). Of these two barriers, the latter is of greater importance for certain unstable small peptides, as these peptides, unless they have been degraded by various proteases, can be transported across the intestinal membrane. Therefore, the use of protease inhibitors is one of the most promising approaches to overcome the delivery problems of these peptides and proteins. Many compounds have been used as protease inhibitors for improving the stability of various peptides and proteins. These include aprotinin, trypsin inhibitors, bacitracin, puromycin, bestatin, and bile salts such as NaCC and are frequently used with absorption enhancers for improvement in rectal absorption. 

---