HAHAHA, HEHEHE, HIHIHI, or HKHKHK : influence of position and composition of histidine containing tags on biodistribution of [(99m)Tc(CO)3](+)-labeled affibody molecules
(2013) In Journal of Medicinal Chemistry 56(12). p.74-4966- Abstract
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 [(99m)Tc(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, lipophilicity promoted liver uptake and decreased... (More)
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 [(99m)Tc(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, lipophilicity 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.
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- author
- Hofström, Camilla ; Altai, Mohamed LU ; Honarvar, Hadis ; Strand, Joanna LU ; Malmberg, Jennie ; Hosseinimehr, Seyed Jalal ; Orlova, Anna ; Gräslund, Torbjörn and Tolmachev, Vladimir
- publishing date
- 2013-06-27
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Cell Line, Tumor, Drug Stability, Female, Histidine, Humans, Hydrophobic and Hydrophilic Interactions, Isotope Labeling, Kinetics, Mice, Organotechnetium Compounds/chemistry, Receptor, ErbB-2/metabolism, Recombinant Fusion Proteins/chemistry, Tissue Distribution
- in
- Journal of Medicinal Chemistry
- volume
- 56
- issue
- 12
- pages
- 74 - 4966
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:84879575076
- pmid:23692562
- ISSN
- 1520-4804
- DOI
- 10.1021/jm400218y
- language
- English
- LU publication?
- no
- id
- 1208982f-c67e-4905-921d-42a2b095ea1a
- date added to LUP
- 2022-11-16 13:42:51
- date last changed
- 2024-04-19 21:01:35
@article{1208982f-c67e-4905-921d-42a2b095ea1a,
abstract = {{<p>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 [(99m)Tc(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, lipophilicity 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. </p>}},
author = {{Hofström, Camilla and Altai, Mohamed and Honarvar, Hadis and Strand, Joanna and Malmberg, Jennie and Hosseinimehr, Seyed Jalal and Orlova, Anna and Gräslund, Torbjörn and Tolmachev, Vladimir}},
issn = {{1520-4804}},
keywords = {{Animals; Cell Line, Tumor; Drug Stability; Female; Histidine; Humans; Hydrophobic and Hydrophilic Interactions; Isotope Labeling; Kinetics; Mice; Organotechnetium Compounds/chemistry; Receptor, ErbB-2/metabolism; Recombinant Fusion Proteins/chemistry; Tissue Distribution}},
language = {{eng}},
month = {{06}},
number = {{12}},
pages = {{74--4966}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of Medicinal Chemistry}},
title = {{HAHAHA, HEHEHE, HIHIHI, or HKHKHK : influence of position and composition of histidine containing tags on biodistribution of [(99m)Tc(CO)3](+)-labeled affibody molecules}},
url = {{http://dx.doi.org/10.1021/jm400218y}},
doi = {{10.1021/jm400218y}},
volume = {{56}},
year = {{2013}},
}