Anticalins as an alternative to antibody technology

Anticalins are a class of engineered ligand-binding proteins that are based on the lipocalin scaffold. The lipocalin protein architecture is characterised by a compact, rigid β-barrel that supports four structurally hypervariable loops. These loops form a pocket for the specific complexation of differing target molecules. Natural lipocalins occur in human plasma and body fluids, where they usually function in the transport of vitamins, steroids or metabolic compounds. Using targeted mutagenesis of the loop region and biochemical selection techniques, variants with novel ligand specificities, both for low-molecular weight substances and for macromolecular protein targets, can be generated. Due to their small size, typically between 160 and 180 residues, robust tertiary structure and composition of a single polypeptide chain, such ‘anticalins’ provide several advantages over antibodies concerning economy of production, stability during storage, faster pharmacokinetics and better tissue penetration. At prese...