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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, Skolan för bioteknologi (BIO), Proteinteknologi.
Vise andre og tillknytning
2013 (engelsk)Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 56, nr 12, s. 4966-4974Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2013. Vol. 56, nr 12, s. 4966-4974
Emneord [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
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Identifikatorer
URN: urn:nbn:se:kth:diva-126896DOI: 10.1021/jm400218yISI: 000321237100012Scopus ID: 2-s2.0-84879575076OAI: oai:DiVA.org:kth-126896DiVA, id: diva2:642856
Forskningsfinansiär
Swedish Research Council
Merknad

QC 20130823

Tilgjengelig fra: 2013-08-23 Laget: 2013-08-22 Sist oppdatert: 2018-01-11bibliografisk kontrollert

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