Avimer

Avimere ( short for Engl. Avidity multimer ) are artificial proteins which are capable of binding antigens. These belong to the group of small antibody mimics proteins were developed by the California biotechnology company Avidia, which has since been acquired by Amgen as potential new drugs.

Structure

Avimere consist of two or more amino acids in length 30 to 35 peptide units, which are structurally derived from the A- domains of different receptors of the cell membrane and are interconnected by means of a linker peptide sequence. Characteristic of these domains is their rigid, stabilized by disulfide bridges and calcium structure. Each of the A domain is able to recognize different surface structures ( epitopes) of a target protein. The combination of domains against different epitopes of one and the same target protein in a Avimer is responsible thanks to the eponymous avidity for the increased binding force to the target protein.

Properties

Avimere consisting of two or three A domains may already exhibit an affinity to their target proteins in the subnanomolar range. In addition, they are characterized as compared to antibodies by an elevated temperature stability. Due to its low molecular mass their plasma half-life is limited, but can be extended by binding to immunoglobulins in vivo.

Production

Starting point for the development of Avimeren against a particular target protein is a molecular library of theoretically possible up to 1023 A- domain peptides. These libraries using appropriate display techniques, such as the phage display selected. The most promising thus selected clones are isolated and are the starting point for a further molecule library, which was extended by a linker and a further A domain per peptide. This molecule library is again selected and extended if necessary. In this way may be obtained from existing Avimere more A domains to different epitopes of a target protein. If the display cycles sequentially performed against various target proteins, so Avimere can be obtained, which bind to different target proteins. This technique has been achieved, for example for a successful extension of the plasma protein half-life of an anti - interleukin-6 Avimers by addition of a anti-immunoglobulin G domain.