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The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry
Here we describe a structure-function analysis of the cell-penetrating peptide Xentry derived from the X-protein of the hepatitis B virus. Remarkably, the tetrapeptide core LCLR retains the cell-penetrating ability of the parental peptide LCLRPVG, as either an L- or D-enantiomer. Substitution of the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014984/ https://www.ncbi.nlm.nih.gov/pubmed/24811205 http://dx.doi.org/10.1038/srep04900 |
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author | Montrose, Kristopher Yang, Yi Krissansen, Geoffrey W. |
author_facet | Montrose, Kristopher Yang, Yi Krissansen, Geoffrey W. |
author_sort | Montrose, Kristopher |
collection | PubMed |
description | Here we describe a structure-function analysis of the cell-penetrating peptide Xentry derived from the X-protein of the hepatitis B virus. Remarkably, the tetrapeptide core LCLR retains the cell-penetrating ability of the parental peptide LCLRPVG, as either an L- or D-enantiomer. Substitution of the cysteine with leucine revealed that the cysteine is essential for activity. In contrast, the C-terminal arginine could be substituted in the L-isomer with lysine, histidine, glutamic acid, glutamine, and asparagine, though the resulting peptides displayed distinct cell-type-specific uptake. Substitution of the leucines in the D-isomer with other hydrophobic residues revealed that leucines are optimal for activity. Surprisingly, linear di- and tetra-peptide forms of Xentry are not cell-permeable. Protease-activatable forms of Xentry were created by fusing Xentry to itself via a protease-cleavable peptide, or by attaching a heparin mimic peptide to the N-terminus. These novel activatable forms of Xentry were only taken up by MCF-7 cells after cleavage by matrix metalloproteinase 9, and could be used to deliver drugs specifically to tumours. |
format | Online Article Text |
id | pubmed-4014984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40149842014-05-13 The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry Montrose, Kristopher Yang, Yi Krissansen, Geoffrey W. Sci Rep Article Here we describe a structure-function analysis of the cell-penetrating peptide Xentry derived from the X-protein of the hepatitis B virus. Remarkably, the tetrapeptide core LCLR retains the cell-penetrating ability of the parental peptide LCLRPVG, as either an L- or D-enantiomer. Substitution of the cysteine with leucine revealed that the cysteine is essential for activity. In contrast, the C-terminal arginine could be substituted in the L-isomer with lysine, histidine, glutamic acid, glutamine, and asparagine, though the resulting peptides displayed distinct cell-type-specific uptake. Substitution of the leucines in the D-isomer with other hydrophobic residues revealed that leucines are optimal for activity. Surprisingly, linear di- and tetra-peptide forms of Xentry are not cell-permeable. Protease-activatable forms of Xentry were created by fusing Xentry to itself via a protease-cleavable peptide, or by attaching a heparin mimic peptide to the N-terminus. These novel activatable forms of Xentry were only taken up by MCF-7 cells after cleavage by matrix metalloproteinase 9, and could be used to deliver drugs specifically to tumours. Nature Publishing Group 2014-05-09 /pmc/articles/PMC4014984/ /pubmed/24811205 http://dx.doi.org/10.1038/srep04900 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Article Montrose, Kristopher Yang, Yi Krissansen, Geoffrey W. The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry |
title | The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry |
title_full | The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry |
title_fullStr | The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry |
title_full_unstemmed | The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry |
title_short | The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: novel activatable forms of Xentry |
title_sort | tetrapeptide core of the carrier peptide xentry is cell-penetrating: novel activatable forms of xentry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014984/ https://www.ncbi.nlm.nih.gov/pubmed/24811205 http://dx.doi.org/10.1038/srep04900 |
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