Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease
A variety of neurodegenerative disorders, including Alzheimer disease (AD), are associated with neurofibrillary tangles composed of the tau protein, as well as toxic tau oligomers. Inhibitors of pathological tau aggregation, interrupting tau self-assembly, might be useful for the development of ther...
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| Format: | Online |
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179029/ |
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pubmed-51790292017-01-04 Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease Dammers, Christina Yolcu, Deniz Kukuk, Laura Willbold, Dieter Pickhardt, Marcus Mandelkow, Eckhard Horn, Anselm H. C. Sticht, Heinrich Malhis, Marwa Nidal Will, Nadja Schuster, Judith Funke, Susanne Aileen Research Article A variety of neurodegenerative disorders, including Alzheimer disease (AD), are associated with neurofibrillary tangles composed of the tau protein, as well as toxic tau oligomers. Inhibitors of pathological tau aggregation, interrupting tau self-assembly, might be useful for the development of therapeutics. Employing mirror image phage display with a large peptide library (over 109 different peptides), we have identified tau fibril binding peptides consisting of d-enantiomeric amino acids. d-enantiomeric peptides are extremely protease stable and not or less immunogenic than l-peptides, and the suitability of d-peptides for in vivo applications have already been demonstrated. Phage display selections were performed using fibrils of the d-enantiomeric hexapeptide VQIVYK, representing residues 306 to 311 of the tau protein, as a target. VQIVYK has been demonstrated to be important for fibril formation of the full lengths protein and forms fibrils by itself. Here, we report on d-enantiomeric peptides, which bind to VQIVYK, tau isoforms like tau3RD (K19) as well as to full lengths tau fibrils, and modulate the aggregation of the respective tau form. The peptides are able to penetrate cells and might be interesting for therapeutic and diagnostic applications in AD research. Public Library of Science 2016-12-22 /pmc/articles/PMC5179029/ /pubmed/28006031 http://dx.doi.org/10.1371/journal.pone.0167432 Text en © 2016 Dammers et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Dammers, Christina Yolcu, Deniz Kukuk, Laura Willbold, Dieter Pickhardt, Marcus Mandelkow, Eckhard Horn, Anselm H. C. Sticht, Heinrich Malhis, Marwa Nidal Will, Nadja Schuster, Judith Funke, Susanne Aileen |
| spellingShingle |
Dammers, Christina Yolcu, Deniz Kukuk, Laura Willbold, Dieter Pickhardt, Marcus Mandelkow, Eckhard Horn, Anselm H. C. Sticht, Heinrich Malhis, Marwa Nidal Will, Nadja Schuster, Judith Funke, Susanne Aileen Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease |
| author_facet |
Dammers, Christina Yolcu, Deniz Kukuk, Laura Willbold, Dieter Pickhardt, Marcus Mandelkow, Eckhard Horn, Anselm H. C. Sticht, Heinrich Malhis, Marwa Nidal Will, Nadja Schuster, Judith Funke, Susanne Aileen |
| author_sort |
Dammers, Christina |
| title |
Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease |
| title_short |
Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease |
| title_full |
Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease |
| title_fullStr |
Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease |
| title_full_unstemmed |
Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease |
| title_sort |
selection and characterization of tau binding ᴅ-enantiomeric peptides with potential for therapy of alzheimer disease |
| description |
A variety of neurodegenerative disorders, including Alzheimer disease (AD), are associated with neurofibrillary tangles composed of the tau protein, as well as toxic tau oligomers. Inhibitors of pathological tau aggregation, interrupting tau self-assembly, might be useful for the development of therapeutics. Employing mirror image phage display with a large peptide library (over 109 different peptides), we have identified tau fibril binding peptides consisting of d-enantiomeric amino acids. d-enantiomeric peptides are extremely protease stable and not or less immunogenic than l-peptides, and the suitability of d-peptides for in vivo applications have already been demonstrated. Phage display selections were performed using fibrils of the d-enantiomeric hexapeptide VQIVYK, representing residues 306 to 311 of the tau protein, as a target. VQIVYK has been demonstrated to be important for fibril formation of the full lengths protein and forms fibrils by itself. Here, we report on d-enantiomeric peptides, which bind to VQIVYK, tau isoforms like tau3RD (K19) as well as to full lengths tau fibrils, and modulate the aggregation of the respective tau form. The peptides are able to penetrate cells and might be interesting for therapeutic and diagnostic applications in AD research. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179029/ |
| _version_ |
1613813017117458432 |