Avimer

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Avimers ( short for avidity multimer ) are artificial proteins that are able to bind antigens . These small proteins, which belong to the group of antibody mimetics , were developed as potential new drugs by the Californian biotechnology company Avidia, which has now been acquired by Amgen .

structure

Avimers consist of two or more 30 to 35 amino acid long peptide units which are structurally derived from the A domains of various receptors on the cell membrane and connected to one another with the aid of a linker peptide sequence. These domains are characterized by their rigid structure, stabilized by calcium and disulfide bridges . Each of the A domains 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 an avimer is responsible for the increased binding force to the target protein thanks to the avidity effect that gives it its name .

properties

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

Manufacturing

The starting point for the development of avimers against a specific target protein is a molecular library with theoretically up to 10 23 possible A-domain peptides. These libraries are selected using appropriate display techniques such as phage display . The most promising clones selected in this way are isolated and are the starting point for a further molecule library, which has been expanded to include a linker and a further A domain per peptide. This molecule library is selected again and expanded if necessary. In this way, avimers consisting of several A domains against different epitopes of a target protein can be obtained. If the display cycles are carried out one after the other against different target proteins, avimers can be obtained which bind to different target proteins. This technique was achieved, for example, for successfully extending the plasma protein half-life of an anti- interleukin-6 avimer by adding an anti- immunoglobulin G domain.

Individual evidence

  1. ↑ a b c Silverman J, Liu Q, Lu Q, et al. : Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains . In: Nat. Biotechnol. . 23, No. 12, December 2005, pp. 1556-61. doi : 10.1038 / nbt1166 . PMID 16299519 .

literature