Anticalins in Drug Development

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Abstract

Anticalins are a novel class of engineered ligand-binding proteins that are prepared from lipocalins – conventional plasma proteins in humans – via targeted random mutagenesis and selection against prescribed haptens or antigens. The first anticalins were selected to bind to small ligands, such as the cardioactive drug digoxin. Recently, libraries that also permit the generation of anticalins with high affinities and specificities for protein targets, especially disease-related cell-surface receptors, have been constructed. Anticalins are much smaller than antibodies or their antigen-binding fragments, lack glycosylation as well as immunological effector functions, and consist of a single, stably folded polypeptide chain. Thus, they offer benefits as biopharmaceuticals in several areas of medical therapy, for example as receptor antagonists or as effective antidotes against toxic compounds.

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