Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
HAHAHA, HEHEHE, HIHIHI, or HKHKHK: Influence of Position and Composition of Histidine Containing Tags on Biodistribution of [Tc-99m(CO)(3)](+)-Labeled Affibody Molecules
KTH, School of Biotechnology (BIO), Protein Technology.
Show others and affiliations
2013 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 56, no 12, 4966-4974 p.Article in journal (Refereed) Published
Abstract [en]

Engineered affibody molecules can be used for high contrast in vivo molecular imaging. Extending a recombinantly produced HER2 binding affibody molecule with a hexa-histidine tag allows for convenient purification by immobilized metal-ion affinity chromatography and labeling with [Tc-99m(CO)(3)](+) but increases radioactivity uptake in the liver. To investigate the impact of charge, lipophilicity, and position on biodistribution, 10 variants of a histidine-based tag was attached to a HER2 binding affibody molecule. The biochemical properties and the HER2 binding affinity appeared to be similar for all variants. In vivo, positive charge promoted liver uptake. For N-terminally placed tags, promoted liver uptake and decreased kidney uptake. Kidney uptake was higher for C-terminally placed tags compared to their N-terminal counterparts. The variant with the amino acid composition HEHEHE placed in the N-terminus gave the lowest nonspecific uptake.

Place, publisher, year, edition, pages
2013. Vol. 56, no 12, 4966-4974 p.
Keyword [en]
affinity chromatography, amino acid sequence, amino terminal sequence, animal experiment, article, binding affinity, binding kinetics, controlled study, drug distribution, drug retention, drug structure, drug uptake, female, in vivo study, isotope labeling, kidney, labeling index, lipophilicity, molecular imaging, mouse, nonhuman, radioactivity
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-126896DOI: 10.1021/jm400218yISI: 000321237100012Scopus ID: 2-s2.0-84879575076OAI: oai:DiVA.org:kth-126896DiVA: diva2:642856
Funder
Swedish Research Council
Note

QC 20130823

Available from: 2013-08-23 Created: 2013-08-22 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textScopus

Authority records BETA

Gräslund, Torbjörn

Search in DiVA

By author/editor
Hofström, CamillaGräslund, Torbjörn
By organisation
Protein Technology
In the same journal
Journal of Medicinal Chemistry
Medicinal Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 69 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf