Influence of Histidine-Containing Tags on the Biodistribution of ADAPT Scaffold Proteins

Bioconjugate Chemistry
Sarah LindboVladimir Tolmachev

Abstract

Engineered scaffold proteins (ESP) are high-affinity binders that can be used as probes for radionuclide imaging. Histidine-containing tags enable both efficient purification of ESP and radiolabeling with (99m)Tc(CO)3. Earlier studies demonstrated that the use of a histidine-glutamate-histidine-glutamate-histidine-glutamate (HE)3-tag instead of the commonly used hexahistidine (H6)-tag reduces hepatic uptake of radiolabeled ESP and short peptides. Here, we investigated the influence of histidine-containing tags on the biodistribution of a novel type of ESP, ADAPTs. A series of anti-HER2 ADAPT probes having H6- or (HE)3-tags in the N-termini were prepared. The constructs, (HE)3-ADAPT6 and H6-ADAPT6, were labeled with two different nuclides, (99m)Tc or (111)In. The labeling with (99m)Tc(CO)3 utilized the histidine-containing tags, while (111)In was attached through a maleimido derivative of DOTA conjugated to the N-terminus. For (111)In-labeled ADAPTs, the use of (HE)3 provided a significantly (p < 0.05) lower hepatic uptake at 1 h after injection, but there was no significant difference in hepatic uptake of (111)In-(HE)3-ADAPT6 and H6-ADAPT6 at later time points. Interestingly, in the case of (99m)Tc, (99m)Tc(CO)3-H6-ADAPT6 provi...Continue Reading

References

Dec 24, 2005·Expert Opinion on Drug Delivery·Vania Kenanova, Anna M Wu
Jun 15, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Torun EngfeldtVladimir Tolmachev
Jul 3, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Torun EkbladVladimir Tolmachev
Nov 11, 2008·Current Pharmaceutical Design·V Tolmachev
Apr 18, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Sara AhlgrenVladimir Tolmachev
Feb 23, 2010·Amino Acids·Zheng MiaoZhen Cheng
May 26, 2010·Current Pharmaceutical Biotechnology·Sara Ahlgren, Vladimir Tolmachev
Jun 3, 2010·Biotechnology Journal·Tove AlmSophia Hober
Oct 13, 2011·PloS One·Johan NilvebrantJohn Löfblom
Jun 28, 2012·Methods in Molecular Biology·Joachim Feldwisch, Vladimir Tolmachev
Nov 28, 2012·European Journal of Nuclear Medicine and Molecular Imaging·Anna OrlovaTorbjörn Gräslund
Jun 4, 2013·Cellular and Molecular Life Sciences : CMLS·Johan NilvebrantSophia Hober
Jun 28, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Matthias EderMichael Eisenhut
Sep 13, 2013·Current Pharmaceutical Design·Mohamed AltaiVladimir Tolmachev
Jan 10, 2014·Expert Opinion on Drug Delivery·Sandra HeskampOtto C Boerman
Mar 13, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Anton G T Terwisscha van ScheltingaShane A Olwill
Mar 14, 2014·European Journal of Nuclear Medicine and Molecular Imaging·Anna OrlovaJohn Löfblom
Mar 26, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jens SörensenHenrik Lindman
Jan 1, 2013·Computational and Structural Biotechnology Journal·Johan Nilvebrant, Sophia Hober
Apr 15, 2014·Molecular Oncology·Emmy D G FleurenOtto C Boerman
Jun 3, 2014·Theranostics·Matthias D'HuyvetterTony Lahoutte
Aug 29, 2014·Expert Review of Proteomics·Shelley E AckermanJennifer R Cochran
Nov 14, 2014·European Journal of Nuclear Medicine and Molecular Imaging·Robert GoldsteinKerry Chester
Dec 2, 2014·International Journal of Oncology·Hadis HonarvarFredrik Y Frejd

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Citations

Jun 25, 2020·EJNMMI Radiopharmacy and Chemistry·Javad GarousiVladimir Tolmachev
Aug 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Kaizong HuangZichun Hua
Oct 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anzhelika VorobyevaJavad Garousi
Jan 20, 2021·Seminars in Cancer Biology·Vladimir TolmachevJens Sörensen
Aug 21, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Olga BraginaVladimir Tolmachev
Sep 3, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Sarah LindboVladimir Tolmachev
Jun 6, 2018·Molecular Pharmaceutics·Sarah LindboVladimir Tolmachev
Aug 22, 2021·Biotechnology Advances·Hèctor López-LagunaUgutz Unzueta

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