Avimer
Avimers (short for pharmaceutical drugs.
Structure
Avimers consist of two or more
disulfide bonds and calcium. Each A domain can bind to a certain epitope of the target protein. The combination of domains binding to different epitopes of the same protein increases affinity to this protein, an effect known as avidity
(hence the name).
Alternatively, the domains can be directed against epitopes on different target proteins. This approach is similar to the one taken in the development of
bispecific monoclonal antibodies. In a study, the plasma half-life of an anti-interleukin 6 avimer could be increased by extending it with an anti-immunoglobulin G domain.[1]
Properties
Avimers with two or three domains can bind to their targets in sub-
heat stability compared with antibodies, but limited plasma half-life
because of their smaller size. Half-life can be increased by binding them to antibodies.
Production
A library theoretically containing up to 1023 different A domains serves as a starting point for the development of avimers.[1] Domains targeting the desired protein are selected with display techniques such as phage display. The most promising species are linked to a second A domain via a short linker peptide, forming a new library. This process can be repeated several times, yielding avimers with an increasing number of domains.
References
- ^ PMID 16299519.
- Jeong, KJ; Mabry, R; Georgiou, G (2005). "Avimers hold their own". Nature Biotechnology. 23 (12): 1493โ4. PMID 16333289.
- Rothe, A; Hosse, RJ; Power, BE (2006). "In vitro display technologies reveal novel biopharmaceutics". The FASEB Journal. 20 (10): 1599โ610. PMID 16873883.
Engineered monoclonal antibodies and antibody mimetics | ||
|---|---|---|
| Whole antibody |  | |
| Fab fragment | ||
| Variable fragment | ||
| Smaller units | ||
| Intracellular | ||
| Antibody mimetics | ||