The Design, Synthesis And Preliminary Activity Assay In Vitro Of Trypsin-like Serine Inhibitor

Trypsin-like Serine proteinase exist in most of the organism, from now on, on account of amino acid sequence, tertiary structure ,catalytic residue sequence (serine residue, histidine residue, aspartic acid residue), has formed 40 different kinds of families. Serine proteinase main conclude: enterokinase ,thrombin, fibrinolysin, tryptase, granzyme, trypsin, kallikrein. All of them have serine residue 195, histidine residue 57, aspartic acid residue 102. In the catalysis progress, hydroxy group of enzyme residue attack the carboxide of peptide, put the peptide hydrolyze into two part. Rencetly has a extensive reseach for them, many of them play a important role in a series of physiological progress, such as digestion, blood clotting, embryonic development, immune response etc. Serine proteinase hydrolysis progress is compose of enzyme precursor and activator. Once the enzyme precursor has been actived, a series of reactions will be happened, will induce irreversible specificity cell responds. For this reason, the proteinase is important to keep stabilization of the organic. Normal organic will synthesize inhibitors to prevent from unhopeful hydrolysis. Such as PI(proteinase inhibitor)come from human body, but for some reason, the level of PI was lower than normal, the balance between of the enzyme and inhibitor were broken, will induce chronic pancreatitis(CP), diffuse intravascular coagulation(DIC).We need exogenous protease inhibitor to prevent and treat inflammation.On account of structural analysis of serine protease inhibitor and binding mode of the enzyme and inhibitor, we design and synthesiz three kinds of trypsinlike serine inhibitor.we remain the guanidino group for pharmacodynamic action group, through...