Inhibition of the serine proteases of the complement system.
Adv Exp Med Biol
; 735: 23-40, 2013.
Article
em En
| MEDLINE
| ID: mdl-23402017
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.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas do Sistema Complemento
/
Inibidores de Serina Proteinase
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Hungria