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  Affibodies – combinatorial binding molecules
Research groups
Summary
Staphylococcal selection
Amyloid beta peptide
In vivo tumor targeting
Targeting of gene therapy vector
Tumor targeting
Affibody 3D-structure
Affibody binding proteins
Biosensor (DNA)
Surface display
In vivo stabilization





This pioneering work on a non-immunoglobulin based framework for affinity protein development was first described in 1995. The new molecules were called affibodies and were based on combinatorial protein engineering of the small and robust a-helical structure of the domains of protein A. Affibody binding proteins have since then found broad use as selective binding reagents in biotechnology applications incl. for example separomics, diagnostics, viral retargeting and in vivo imaging (see refs below). Structures of affibody-target co-complexes have been solved by both x-ray crystallography and NMR. In parallel to the use of phage display technology, new selection systems for affibody libraries have also been developed both based on Gram positive bacteria, FACS-sorting of micro beads and protein fragment complementation assays (PCA).

Key (own) publications:
Nygren, P.-Å. (2008) "Alternative binding proteins: Affibody binding proteins developed from a small three-helix bundle scaffold" FEBS Journal 275, 2668-2676.
Hoyer W, Grönwall C, Jonsson A, Ståhl S, Härd T. "Stabilization of a beta-hairpin in monomeric Alzheimer's amyloid-beta peptide inhibits amyloid formation" Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5099-104.
Renberg, B., Nordin, J. Merca, A., Uhlén, M., Feldwisch, J., Nygren, P.-Å. and Eriksson Karlström, A. (2007) "Affibody molecules in protein capture microarrays. evaluation of multidomain ligands and different detection formats" J. Proteome Res. 6, 171-179.
Nilsson FY, Tolmachev V. "Affibody molecules: new protein domains for molecular imaging and targeted tumor therapy" Curr Opin Drug Discov Devel. 2007 Mar;10(2):167-75.
Tolmachev V, Orlova A, Nilsson FY, Feldwisch J, Wennborg A, Abrahmsén L. "Affibody molecules: potential for in vivo imaging of molecular targets for cancer therapy" Expert Opin Biol Ther. 2007 Apr;7(4):555-68.
Renberg, B., Nygren, P.-Å., Eklund, M. and Eriksson Karlström, A. (2004) "Fluorescence resonance energy transfer-based detection of analytes using anti-idiotypic affinity protein pairs" Anal. Biochem. 334, 72-80.
Engfeldt, T., Renberg B., Brumer, H., Nygren, P.-Å. and Eriksson Karlström, A. "Chemical synthesis of fluorescent-labeled affinity proteins for specific binding and detection of unlabeled protein" Chem. BioChem. 6, 1043-1050.
Renberg, B., Shiroyama, I., Engfeldt, T., Nygren, P.-Å. and Eriksson Karlström, A. (2005) "Affibody protein capture microarrays: synthesis and evaluation of random and directed immobilization of affibody molecules" Anal. Biochem. 334, 72-80.
Nygren, P.-Å and Skerra A. (2004) "Binding proteins from alternative scaffolds" J. Immunol. Meth. 290, 3-28.
Wahlberg, E., Lendel, C., Helgstrand, M., Allard, P., Dincbas-Renqvist, V., Hedqvist, A., Berglund, H., Nygren, P.-Å. and Härd, T. (2003) "An affibody in complex with a target protein: structure and coupled folding" Proc. Natl. Acad. Sci. U.S.A. 100, 3185-3190.
Högbom, M., Eklund, M., Nygren, P.-Å. and Nordlund P. (2003) "Crystal structure of an in vitro evolved affibody-protein complex" Proc. Natl. Acad. Sci. U.S.A. 100, 3191-3196.
Rönnmark, J, Kampf, C., Asplund, A., Höidén-Guthenberg, Wester, K., I-M, Pontén, F., Uhlén, M. and Nygren, P.-Å. (2003)"Affibody-β-galactosidase immunoconjugates produced as soluble fusion proteins in the E. coli cytosol". J. Immunol. Meth. 281, 149-160.
Rönnmark, J., Hansson, M., Nguyen, T., Uhlén, M., Robert, A., Ståhl, S. and Nygren, P.-Å. (2002) "Construction and characterization of affibody-Fc chimeras produced in Escherichia coli" J. Immunol. Meth. 261, 199-211.
Karlström, A. and Nygren, P.-Å. [2001] "Dual labeling of a binding protein allows for specific fluorescence detection of native protein" J. Anal. Biochem. 295, 22-30.
Nord, K., Gunneriusson, E., Uhlén, M. and Nygren, P.-Å. (2000) "Ligands selected from combinatorial libraries of protein a for use in affinity capture of apolipoprotein A-1 and Taq DNA polymerase" J. Biotechnol. 80, 45-54.
Eklund, Axelsson, Uhlen & Nygren Anti-idiotypic protein domains selected from protein A-based affibody libraries. Proteins 48, 454-462 (2002).
Nord et al. Recombinant human factor VIII-specific affinity ligands selected from phage-displayed combinatorial libraries of protein A. Eur J Biochem 268, 4269-4277 (2001).
Gunneriusson, Nord, Uhlen & Nygren Affinity maturation of a Taq DNA polymerase specific affibody by helix shuffling. Protein Eng 12, 873-878 (1999).
Nygren & Uhlen Scaffolds for engineering novel binding sites in proteins. Curr Opin Struct Biol 7, 463-469 (1997).
Nord et al. Binding proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain. Nature Biotechnol 15, 772-777 (1997).
Nord, Nilsson, Nilsson, Uhlen & Nygren A combinatorial library of an alpha-helical bacterial receptor domain. Protein Eng 8, 601-608 (1995).
Last updated: 2008-06-05