体内分布
化学
亲脂性
组氨酸
体内
分子
氨基酸
立体化学
生物化学
体外
有机化学
生物技术
生物
作者
Camilla Hofström,Mohamed Altai,Hadis Honarvar,Joanna Strand,Jennie Malmberg,Seyed Jalal Hosseinimehr,Anna Orlova,Torbjörn Gräslund,Vladimir Tolmachev
摘要
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 [99mTc(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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