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Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide
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 co...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991022/ https://www.ncbi.nlm.nih.gov/pubmed/27713244 http://dx.doi.org/10.3390/ph3010110 |
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author | Khaja, Khaleel Robbins, Paul |
author_facet | Khaja, Khaleel Robbins, Paul |
author_sort | Khaja, Khaleel |
collection | PubMed |
description | 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 IκB 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-κB 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. |
format | Online Article Text |
id | pubmed-3991022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Molecular Diversity Preservation International |
record_format | MEDLINE/PubMed |
spelling | pubmed-39910222014-04-18 Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide Khaja, Khaleel Robbins, Paul Pharmaceuticals (Basel) Article 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 IκB 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-κB 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. Molecular Diversity Preservation International 2010-01-08 /pmc/articles/PMC3991022/ /pubmed/27713244 http://dx.doi.org/10.3390/ph3010110 Text en © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Khaja, Khaleel Robbins, Paul Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide |
title | Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide |
title_full | Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide |
title_fullStr | Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide |
title_full_unstemmed | Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide |
title_short | Comparison of Functional Protein Transduction Domains Using the NEMO Binding Domain Peptide |
title_sort | comparison of functional protein transduction domains using the nemo binding domain peptide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991022/ https://www.ncbi.nlm.nih.gov/pubmed/27713244 http://dx.doi.org/10.3390/ph3010110 |
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