One of the characteristics of Alzheimer's disease is the presence of neurotoxicdeposits in brain tissues, which are largely made up of a short peptide referred to as A?? Theelucidation of the factors responsible for the formation and stabilization of pathologically relevantfibrils is important for designing preventive and therapeutic agents to combat the disease.
We aim to investigate one specific aspect of the fibril stabilization process as part of the overall fibrilstability picture, namely the role of individual non-polar side chains located in the hydrophobicinterior of the fibrils. Thus, our studies will complement global investigations into stability byrevealing the most important local sites, which can then become targets for the design ofmodifications, ligands, and mutants that disrupt the stabilization of the fibrils. Our tools will allowfor a balanced view of kinetic and thermodynamic stabilization at the selected sites. We will studytwo different morphologies of the wild-type peptide as well as a mutant associated with the earlyonset of the disease. We will utilize deuterium nuclear magnetic resonance spectroscopy andcomputational modeling to achieve this goal.
Alzheimer's disease is characterized by toxic deposits (plaques) in braintissue. Our project investigates one of the mechanisms that may be involved in the stabilizationand formation of these plaques. In particular; we will study how specific molecular segments maycontribute to this process; which would be useful for the design of preventative and therapeuticagents that combat the disease.
| Vugmeyster, Liliya; Griffin, Aaron; Ostrovsky, Dmitry et al. (2018) Correlated motions of C'-N and C?-C? pairs in protonated and per-deuterated GB3. J Biomol NMR 72:39-54 |
| Vugmeyster, Liliya; Ostrovsky, Dmitry (2018) Basic experiments in 2H static NMR for the characterization of protein side-chain dynamics. Methods 148:136-145 |
| Vugmeyster, Liliya; Ostrovsky, Dmitry; Hoatson, Gina L et al. (2017) Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by 2H NMR Relaxation. J Phys Chem B 121:7267-7275 |
| Vugmeyster, Liliya; Ostrovsky, Dmitry (2017) Comparative Dynamics of Methionine Side-Chain in FMOC-Methionine and in Amyloid Fibrils. Chem Phys Lett 673:108-112 |
| Vugmeyster, Liliya; Ostrovsky, Dmitry (2017) Static solid-state 2H NMR methods in studies of protein side-chain dynamics. Prog Nucl Magn Reson Spectrosc 101:1-17 |
| Vugmeyster, Liliya; Ostrovsky, Dmitry; Clark, Matthew A et al. (2016) Fast Motions of Key Methyl Groups in Amyloid-? Fibrils. Biophys J 111:2135-2148 |
| Vugmeyster, Liliya; Clark, Matthew A; Falconer, Isaac B et al. (2016) Flexibility and Solvation of Amyloid-? Hydrophobic Core. J Biol Chem 291:18484-95 |
| Vugmeyster, Liliya; Ostrovsky, Dmitry; Villafranca, Toni et al. (2015) Dynamics of Hydrophobic Core Phenylalanine Residues Probed by Solid-State Deuteron NMR. J Phys Chem B 119:14892-904 |
