@article {Olubiyi:2014:0929-8673:1448,
title = "Amyloid Aggregation Inhibitory Mechanism of Arginine-rich D-peptides",
journal = "Current Medicinal Chemistry",
parent_itemid = "infobike://ben/cmc",
publishercode ="ben",
year = "2014",
volume = "21",
number = "12",
publication date ="2014-04-01T00:00:00",
pages = "1448-1457",
itemtype = "ARTICLE",
issn = "0929-8673",
url = "https://www.ingentaconnect.com/content/ben/cmc/2014/00000021/00000012/art00005",
keyword = "Amyloid beta, in silico, amyloid inhibition, ThT assay, D-peptides, surface plasmon resonance",
author = "Olubiyi, O.O. and Frenzel, D. and Bartnik, D. and Gluck, J.M. and Brener, O. and Nagel-Steger, L. and Funke, S.A. and Willbold, D. and Strodel, B.",
abstract = "It is widely believed that Alzheimer's disease pathogenesis is driven by the production and deposition of the amyloid- peptide (A) in the brain. In this study, we employ a combination of in silico and in vitro approaches to investigate the inhibitory properties of selected
arginine-rich D-enantiomeric peptides (D-peptides) against amyloid aggregation. The D-peptides include D3, a 12-residue peptide with anti-amyloid potencies demonstrated in vitro and in vivo, RD2, a scrambled sequence of D3, as well as truncated RD2 variants. Using a global optimization method
together with binding free energy calculations followed by molecular dynamics simulations, we perform a detailed analysis of D-peptide binding to A monomer and a fibrillar A structure. Results obtained from both molecular simulations and surface plasmon resonance experiments reveal
a strong binding of D3 and RD2 to A, leading to a significant reduction in the amount of structures in both monomer and fibril, which was also demonstrated in Thioflavin T assays. The binding of the D-peptides to A is driven by electrostatic interactions, mostly involving the
D-arginine residues and Glu11, Glu22 and Asp23 of A. Furthermore, we show that the anti-amyloid activities of the D-peptides depend on the length and sequence of the Dpeptide, its ability to form multiple weak hydrophobic interactions with A, as well as the A oligomer size.",
}