TY  - JOUR
AU  - Dammers, Christina
AU  - Yolcu, Deniz
AU  - Kukuk, Laura
AU  - Willbold, Dieter
AU  - Pickhardt, Marcus
AU  - Mandelkow, Eckhard
AU  - Horn, Anselm H. C.
AU  - Sticht, Heinrich
AU  - Malhis, Marwa Nidal
AU  - Will, Nadja
AU  - Schuster, Judith
AU  - Funke, Aileen
TI  - Selection and Characterization of Tau Binding D-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease
JO  - PLoS one
VL  - 11
IS  - 12
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - FZJ-2017-00417
SP  - e0167432
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000392843200017
C6  - pmid:28006031
DO  - DOI:10.1371/journal.pone.0167432
UR  - https://juser.fz-juelich.de/record/826171
ER  -