Affilins are artificial proteins designed to selectively bind antigens. Affilin proteins are structurally derived from human ubiquitin (historically also from gamma-B crystallin). Affilin proteins are constructed by modification of surface-exposed amino acids of these proteins and isolated by display techniques such as phage display and screening. They resemble antibodies in their affinity and specificity to antigens but not in structure, which makes them a type of antibody mimetic. Affilin was developed by Scil Proteins GmbH as potential new biopharmaceutical drugs, diagnostics and affinity ligands. Structure Two proteins, gamma-B crystallin and ubiquitin, have been described as scaffolds for Affilin proteins. Certain amino acids in these proteins can be substituted by others without losing structural integrity, a process creating regions capable of binding different antigens, depending on which amino acids are exchanged. In both types, the binding region is typically located in a beta sheet structure, whereas the binding regions of antibodies, called complementarity-determining regions, are flexible loops. Based on gamma crystallin Historically, Affilin molecules were based on gamma crystallin, a family of proteins found in the eye lens of vertebrates, including humans. It consists of two identical domains with mainly beta sheet structure and a total molecular mass of about 20 kDa. The eight surface-exposed amino acids 2, 4, 6, 15, 17, 19, 36, and 38 are suitable for modification. Based on ubiquitin Ubiquitin, as the name suggests, is a highly conserved protein occurring ubiquitously in eukaryotes. It consists of 76 amino acids in three and a half alpha helix windings and five strands constituting a beta sheet. For example, the eight surface-exposed exchangeable amino acids 2, 4, 6, 62, 63, 64, 65, and 66 are located at the beginning of the first N-terminal beta strand (2, 4, 6), at the nearby beginning of the C-terminal strand and the loop leading up to it (63–66). The resulting Affilin proteins are about 10 kDa in mass. Properties The molecular mass of crystallin and ubiquitin based Affilin proteins is only one eighth or one sixteenth of an IgG antibody, respectively. This leads to an improved tissue permeability, heat stability up to 90 °C (195 °F), and stability towards proteases as well as acids and bases. The latter enables Affilin proteins to pass through the intestine, but like most proteins they are not absorbed into the bloodstream. Renal clearance, another consequence of their small size, is the reason for their short plasma half-life, generally