Affilin

Edit links
Source: Wikipedia, the free encyclopedia.
gamma-B crystallin (PDB: 2JDG
​)

Affilins are artificial

antibodies in their affinity and specificity to antigens but not in structure,[1] which makes them a type of antibody mimetic. Affilin was developed by Scil Proteins GmbH as potential new biopharmaceutical drugs, diagnostics and affinity ligands.[2]

Structure

Human gamma-B crystallin, wild-type (PDB: 2JDF​). The beta strands making up the beta sheets are coloured blue.

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,[1][3] whereas the binding regions of antibodies, called complementarity-determining regions, are flexible loops.[4]

Based on gamma crystallin

Historically, Affilin molecules were based on

kDa.[5] The eight surface-exposed amino acids 2, 4, 6, 15, 17, 19, 36, and 38 are suitable for modification.[6]

Based on ubiquitin

C-terminal
strand is the one in front, pointing right and downwards. The exchangeable amino acids are located at the top left.

C-terminal strand and the loop leading up to it (63–66). The resulting Affilin proteins are about 10 kDa in mass.[7]

Properties

The molecular mass of crystallin and ubiquitin based Affilin proteins is only one eighth or one sixteenth of an

clearance, another consequence of their small size, is the reason for their short plasma half-life, generally a disadvantage for potential drugs.[1]

Production

Molecular libraries of Affilin proteins are generated by randomizing sets of amino acids by

disulfide bonds. In an Affilin protein comprising two modified ubiquitin molecules, for example, up to 14 amino acids are exchanged,[8]
resulting in 8 × 1017 combinations, but not all of these are realized in a given library.

The next step is the selection of Affilin proteins that bind the desired target protein. To this end display techniques such as phage display or

diagnostics. Conjugation of cytokines has also been tested in vitro.[9]

Large-scale production of Affilin proteins is facilitated by

E. coli and other organisms commonly used in biotechnology.[1]

References

  1. ^
    PMID 17628592
    .
  2. PMID 16054718
    .
  3. ^
    PMID 3041007
    .
  4. ISBN 0-7216-0008-5
    .
  5. PMID 11724156
    .
  6. ^ WO 0104144  Fabrication of beta-plated sheet proteins with specific binding properties. Fiedler, U.; Rudolph, R. Publication date: 2001-01-18.
  7. ^ WO 2006040129  Protein conjugates for use in therapy, diagnosis and chromatography. Fiedler, E.; Ebersbacher, H.; Hey, Th.; Fiedler, U. / Scil Proteins GmbH. Publication date: 2006-04-20.
  8. ^ "Affilin Scaffold". Scil Proteins. Retrieved 2010-07-29.
  9. ^ "Affilin Conjugates". Scil Proteins. Retrieved 2010-07-29.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Affilin&oldid=1125459816"