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Selection and characterization of HER2/neu-binding affibody ligands

Wikman, Maria (author)
KTH,Bioteknologi
Steffen, Ann-Charlott (author)
Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
Gunneriusson, Elin (author)
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Tolmachev, Vladimir (author)
Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
Adams, Gregory P. (author)
Fox Chase Cancer Center
Carlsson, Jörgen (author)
Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
Ståhl, Stefan (author)
KTH,Bioteknologi
Adams, Gregg (author)
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 (creator_code:org_t)
2004-06-08
2004
English.
In: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 17:5, s. 455-462
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Affibody (affibody) ligands that are specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) have been selected by phage display technology from a combinatorial protein library based on the 58 amino acid residue staphylococcal protein A-derived Z domain. The predominant variants from the phage selection were produced in Escherichia coli, purified by affinity chromatography, and characterized by biosensor analyses. Two affibody variants were shown to selectively bind to the extracellular domain of HER2/neu (HER2-ECD), but not to control proteins. One of the variants, denoted His6-ZHER2/neu:4, was demonstrated to bind with nanomolar affinity (approximately 50 nM) to the HER2-ECD molecule at a different site than the monoclonal antibody trastuzumab. Furthermore, radiolabeled His6-ZHER2/neu:4 affibody showed specific binding to native HER2/neu, overexpressed on the SKBR-3 tumor cell line. Such affibody ligands might be considered in tumor targeting applications for radionuclide diagnostics and therapy of adenocarcinomas such as breast and ovarian cancers.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Amino Acid Sequence
Antibodies; Monoclonal/pharmacology
Antineoplastic Agents/pharmacology
Biosensing Techniques
Humans
Iodine Radioisotopes
Ligands
Molecular Sequence Data
Protein Structure; Secondary
Receptor; erbB-2/antagonists & inhibitors/genetics/*metabolism
Research Support; Non-U.S. Gov't
Time Factors
MEDICINE
MEDICIN
Microbiology

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art (subject category)

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