Effects of serine protease inhibitor

Nakatani K, Takeshita S, Tsujimoto H, Kawamura Y, Sekine I. Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury. J Leukoc Biol 2001 ... 

Induction of mRNAs for several other specific rat hepatic proteins by GH has also been demonstrated [81-83]. The effect could be demonstrated in vivo and in vitro and involved a relatively rapid induction with a 5-fold increase in mRNA levels within 4 h of the administration of GH, although synergism with cortisol (possibly and/or thyroxine) was necessary for a maximal response [83]. cDNAs corresponding to two of the induced proteins have been cloned [82,83] and found to have sequences homologous to those of a known family of serine protease inhibitors. One of these proteins was shown to be secreted as a heavily glycosylated serum protein, and to have potent anti-trypsin activity [83]. Regulation of the production of this protein by GH was shown to occur mainly at the transcriptional level [83]. 

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. 

Indeed, the structural requirement for the interaction of these SPs with the coagulation cofactors and their target proteases and inhibitors are stereospecific (Mourao, 2004 Mourao and Pereira, 1999 Pomin, 2008 Pomin and Mourao, 2008). The site of sulfation has a major impact on activity. This can be illustrated by the fact that 2,4-di-sulfated units have an amplifying effect on the AT-mediated anticoagulant activity in the series of 3-linked a-L-fucans (Fig. 12.1 Table 12.1). Specific sulfation sites are required for the interaction with plasma serine-protease inhibitors. Note the occurrence of the 4-sulfated unit content in the... 

Diazetidin-2,4-dione has been found to be a chymase inhibitor (IC50 4.0nM). It has been found that 1,3-diazetidin-2,4-dione derivatives possess high activities against bovine pancreatic cr-chrymotrypsin, human cathepsin G, and human neutrophil elastase. Some of the derivatives of l,3-diazetidin-2,4-diones have been shown to be effective as a scaffold for serine protease inhibitors <2001BML1691>. Further, 1,3-diazetidinone containing scaffolds have been found to possess potential antibacterial properties (Section 2.13.7.3). 

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