title: Inhibition of the serine proteases of the complement system.
abstract: Proteases play important roles in human physiology and pathology. The complement system is a proteolytic cascade, where serine proteases activate each other by limited proteolysis in a strictly ordered manner. Serine proteases are essential in both the initiation and the amplification of the cascade. Since uncontrolled complement activation contributes to the development of serious disease conditions, inhibition of the complement serine proteases could be an attractive therapeutic approach. In this chapter, we give a brief overview of the major types of natural serine protease inhibitors and their role in controlling the complement cascade. A special emphasis is laid on C1-inhibitor, a natural complement protease inhibitor, which is approved for clinical use in hereditary angioedema (HAE). We also examine the potential of developing artificial complement protease inhibitors. Synthetic small-molecule drugs can be very efficient serine protease inhibitors, but they usually lack sufficient specificity. A promising approach to yield more specific compounds is the alteration of natural protease inhibitors through engineering or directed evolution resulting in new variants with fine-tuned specificity and enhanced affinity.
authors: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. gal@enzim.hu
authors: Péter
authors: P
authors: Gál
authors: József
authors: J
authors: Dobó
authors: László
authors: L
authors: Beinrohr
authors: Gábor
authors: G
authors: Pál
authors: Péter
authors: P
authors: Závodszky
mesh_terms: D000818:Animals; D050718:Complement C1 Inhibitor Protein / Q000494:pharmacology; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D015202:Protein Engineering; D057057:Serine Proteases / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D054852:Small Molecule Libraries
chemical_list: D050718:Complement C1 Inhibitor Protein; D015842:Serine Proteinase Inhibitors; D054852:Small Molecule Libraries; D003165:Complement System Proteins; D057057:Serine Proteases