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Inhibition of the Serine Proteases of the Complement System

  • Péter GálEmail author
  • József Dobó
  • László Beinrohr
  • Gábor Pál
  • Péter Závodszky
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)

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.

Keywords

Serine Protease Hereditary Angioedema Lectin Pathway Plasma Kallikrein Reactive Center Loop 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the Ányos Jedlik grant NKFP_07_1-MASPOK07, the Hungarian Scientific Research Fund (OTKA) grant NK77978, NK100834, K68408, NK81950 and NK100769 and the NDA grant KMOP-1.1.2-07/1-2008-0003 and the National Development Agency Grant KMOP-1.1.2-07/1-2008-0003 as well as by the European Union and the European Social Fund (TÁMOP) 4.2.1./B-09/KMR-2010-0003 grant.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Péter Gál
    • 1
    Email author
  • József Dobó
    • 1
  • László Beinrohr
    • 1
  • Gábor Pál
    • 2
  • Péter Závodszky
    • 1
  1. 1.Institute of Enzymology, Research Centre for Natural SciencesHungarian Academy of SciencesBudapestHungary
  2. 2.Department of BiochemistryEötvös Loránd UniversityBudapestHungary

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