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Intracellular MR Contrast Agents based on l-Tat and d-Tat: A Comparative Study

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons84244

Su,  W
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons84085

Mishra,  R
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons83903

Engelmann,  J
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons84137

Pfeuffer,  J
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Citation

Su, W., Mishra, R., Engelmann, J., Pfeuffer, J., & Ugurbil, K. (2005). Intracellular MR Contrast Agents based on l-Tat and d-Tat: A Comparative Study. Poster presented at COST Chemistry Action D18: Lanthanide Chemistry for Diagnosis and Therapy, Köln, Germany.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0013-D463-8
Abstract
However, a unique class of peptides known as cell penetrating peptides (CPPs) has the ability to traverse this barrier and convey cargo molecules attached to it across the cell membrane [1]. CPPs are short peptides (generally less than 30 residues) with net positive charge and acting in a receptor- and energy-independent manner. Amongst a variety of natural and chimeric CPPs, HIV-1 tat protein derived Tat peptide (Tat ) has received much attention mainly because of its high efficiency to deliver a 49-57 large variety of cargo molecules across the membrane. Noninvasive imaging techniques like MRI possess the prospective to observe molecular-genetic and cellular processes. The combination of these exogenously administered molecular imaging agents with CPPs may enhance their intracellular delivery, thus solving several queries at sub-cellular level. Improved cellular uptake of the unnatural retro-inverso isomer of Tat, d-Tat57-49 (rrrqrrkkr), has been reported in comparison to l-Tat (RKKRRQRRR) [2]. 49-57 Considering the potential of Tat as a molecular transporter, we coupled l-Tat and d- 49-57 Tat with fluorescence imaging agent FITC as well as with MR agent Gd-DTPA, 57-49 thus obtaining l-Tat-Lys(FITC)-(Gd)DTPA (l-Tat CA) and d-Tat-ys(FITC)-(Gd)DTPA (d-Tat CA), respectively. Based on optical imaging and relaxation time measurements we compared cellular internalization and contrast enhancement efficiencies of these two bimodal cell internalizing contrast agents.