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Binding proteins internalized by PTD-fused ligands allow the intracellular sequestration of selected targets by ligand exchange

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The targeted inactivation of intracellular molecules has important therapeutic potential. For this purpose, it could be envisioned to introduce specifically designed binding proteins into cells by covalent linkage to protein transduction domains (PTDs). However, stable linkage of a PTD to a cargo may affect its conformation and, hence, its binding property inside the cell. Here, we analyzed the ability of non-covalently linked PTDs to internalize the model binding proteins streptavidin (SA) and Strep-Tactin (ST). Notably, inside the cell, the PTD-Strep-tag II ligand used for internalization of SA was displaced by the model target biotin which exhibits a higher binding affinity for the same binding pocket. Thus, specifically designed binding proteins can be internalized into cells by non-covalent binding to a PTD and subsequently be used for capturing given intracellular target molecules by ligand exchange. Under therapeutic aspects, it could be envisioned to further develop such systems for the intracellular sequestration, and consequently, functional inactivation of pathologically relevant factors.
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Document Type: Research Article

Affiliations: Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany., Email: [email protected]

Publication date: April 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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