Kunitz domain
Kunitz domains are protease- inhibiting protein domains of protease inhibitors of the Kunitz type, such as the Bovine Pancreatic Trypsin Inhibitor (BPTI, Aprotinin ), the Tissue Factor Pathway Inhibitor (TFPI), the Alzheimer's amyloid β-protein precursor (APPI) and the Inter-α-trypsin inhibitor . Kunitz domains, which are about 60 amino acids in length , are themselves stable proteins and can inhibit proteases such as trypsin , chymotrypsin and kallikrein . Therefore, Kunitz domains are a popular backbone for the development of new drugs . With Ecallantid , the first Kunitz domain peptide was approved as a drug in the USA in 2009 .
Drug development
The interest of the pharmaceutical industry in Kunitz domains for the development of biopharmaceuticals is based on their ability to selectively recognize protein structures. This property, which is common to other antibody mimetics , is supplemented by their ability to bind to the active site of an enzyme, combined with competitive, reversible inhibition. With the help of display techniques such as phage display , suitable domains are selected from molecule libraries that contain over 10 million different variants of Kunitz domains. After characterization and optimization of selected domains, large-scale production can take place with the help of production organisms commonly used in biotechnology . In this way, for example, the kallikrein inhibitor ecallantide and the neutrophil elastase inhibitor Depelestat could be found.
Individual evidence
- ↑ Dyax Corp .: Full prescibing information Kalbitor (PDF; 169 kB) 2009. Retrieved on 2 May, 2010.
literature
- Nixon AE, Wood CR: Engineered protein inhibitors of proteases . In: Curr Opin Drug Discov Devel . 9, No. 2, March 2006, pp. 261-8. PMID 16566296 .