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Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
* Author to whom correspondence should be addressed.
Received: 24 October 2009; in revised form: 22 December 2009 / Accepted: 24 December 2009 / Published: 8 January 2010
Abstract: Protein transduction domains (PTDs), both naturally occurring and synthetic, have been extensively utilized for intracellular delivery of biologically active molecules both in vitro and in vivo. However, most comparisons of transduction efficiency have been performed using fluorescent markers. To compare efficiency of functional protein transduction, a peptide derived from IkB kinase ß (IKKß) that prevents formation of an active IKK complex was used as a biologically active cargo. This peptide, termed NEMO Binding Domain (NBD), is able to block activation of the transcriptional factor NF-κB by IKK, but not basal NF-κB activity. Our results demonstrate that Antp and Tat PTDs were most effective for delivery of NBD for inhibition of NF-kB activation compared to other PTD-NBD in both Hela and 293 cells, however, at higher concentrations (100 µM), the Antp-NBD as well as the FGF-NBD peptide caused significant cellular toxicity. In contrast to the cell culture results, delivery of NBD using 8K (octalysine) and 6R (six arginine) were the most effect in blocking inflammation following local, footpad delivery in a KLH-induced DTH murine model of inflammatory arthritis. These results demonstrate differences between PTDs for delivery of a functional cargo between cell types.
Keywords: protein transduction domains; NEMO-binding domain; NF-kB; delayed type hypesenDTH; arthritis
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Khaja, K.; Robbins, P. Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide. Pharmaceuticals 2010, 3, 110-124.
Khaja K, Robbins P. Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide. Pharmaceuticals. 2010; 3(1):110-124.
Khaja, Khaleel; Robbins, Paul. 2010. "Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide." Pharmaceuticals 3, no. 1: 110-124.