Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease

Dammers C, Yolcu D, Kukuk L, Willbold D, Pickhardt M, Mandelkow E, Horn A, Sticht H, Malhis MN, Will N, Schuster J, Funke SA (2016)

Publication Type: Journal article

Publication year: 2016

Journal

PLoS ONE Public Library of Science

Book Volume: 11

Journal Issue: 12

DOI: 10.1371/journal.pone.0167432

Abstract

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.

Authors with CRIS profile

Anselm Horn Professur für Bioinformatik Heinrich Sticht Professur für Bioinformatik

Involved external institutions

Hochschule für angewandte Wissenschaften Coburg DE Germany (DE) Forschungszentrum Jülich / Research Centre Jülich (FZJ) DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE)

How to cite

APA:

Dammers, C., Yolcu, D., Kukuk, L., Willbold, D., Pickhardt, M., Mandelkow, E.,... Funke, S.A. (2016). Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease. PLoS ONE, 11(12). https://doi.org/10.1371/journal.pone.0167432

MLA:

Dammers, Christina, et al. "Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease." PLoS ONE 11.12 (2016).

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