Journal article

Publication year: 2017

Pages: 4840-4849

Journal: Biochemistry

Volume number: 56

Issue number: 36

ISSN: 0006-2960

DOI Link: https://doi.org/10.1021/acs.biochem.7b00223

Publisher: American Chemical Society

Abstract: 
The peptide sequence KLVFF resembles the hydrophobic core of the A beta peptide known to form amyloid plaques in Alzheimer's disease. Starting from its retro-inverso peptide, we have synthesized three generations of peptidomimetics. Step by step natural amino acids have been replaced by aromatic building blocks accessible from the Pd-catalyzed Catellani reaction. The final compound 18 is stable against proteolytic decay and largely prevents the aggregation of A beta(1-42) overextended periods of time. The activity of the new inhibitors was tested first by fluorescence correlation spectroscopy. For closer examination of compound 18, additional techniques were also applied: laser-induced liquid bead ion desorption mass spectrometry, confocal laser scanning microscopy, thioflavin T fluorescence, and gel electrophoresis. Compound 18 not only retards the aggregation of chemically synthesized A beta but also can partially dissolve the oligomeric structures. Thioflavin binding mature fibrils, however, seem to resist the inhibitor.

Harvard Citation style: Stark, T., Lieblein, T., Pohland, M., Kalden, E., Freund, P., Zangl, R., et al. (2017) Peptidomimetics That Inhibit and Partially Reverse the Aggregation of A beta(1-42), Biochemistry, 56(36), pp. 4840-4849. https://doi.org/10.1021/acs.biochem.7b00223

APA Citation style: Stark, T., Lieblein, T., Pohland, M., Kalden, E., Freund, P., Zangl, R., Grewal, R., Heilemann, M., Eckert, G., Morgner, N., & Göbel, M. (2017). Peptidomimetics That Inhibit and Partially Reverse the Aggregation of A beta(1-42). Biochemistry. 56(36), 4840-4849. https://doi.org/10.1021/acs.biochem.7b00223