Details

Autor(en) / Beteiligte

• Kolln, Johanna
• Spillner, Edzard
• Andra, Jorg
• Klensang, Katrin
• Bredehorst, Reinhard

Titel

Complement Inactivation by Recombinant Human C3 Derivatives

Ist Teil von

• The Journal of immunology (1950), 2004-11, Vol.173 (9), p.5540-5545

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2004

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• From the implications of the complement system in a large number of diseases, an urgent need for therapeutics effecting reduced complement activity in vivo has emerged. In this study we report the design of a novel class of enzymes of human origin that obliterate functional complement by a noninhibitory, catalytic mechanism. Combining the framework of human C3 and the enzymatic mechanism of cobra venom factor, a nontoxic snake venom protein, we established molecules capable of forming stable C3 convertase complexes. Although the half-life of naturally occurring C3 convertase complexes ranges between 1 and 2 min, these complexes exhibit a half-life of up to several hours. Because the overall identity to human C3 could be extended to >90%, the novel C3 derivatives can be assumed to exhibit low immunogenicity and, therefore, represent promising candidates for therapeutic reduction of complement activity in vivo.