An FT-IR study of the beta-amyloid conformation: standardization of aggregation grade.
The aggregation of beta-amyloid peptides is very important for their neurotoxic effect; standardization of the aggregation grade is necessary for biological experiments. Measurement of aggregation with physicochemical methods is a difficult task. The present work revealed that FT-IR can be used for studying the aggregation properties of beta-amyloid peptides and the effects of environmental variables (solvent, pH, ions, and temperature) on aggregation. In dimethyl sulfoxide or hexafluoroisopropanol, amyloid peptides are in a monomeric state; on dilution with phosphate buffer just before measurement is made, aggregation begins. A detailed two-dimensional FT-IR correlation spectroscopic study was made of the conformational transitions that occur during the aggregation of beta-amyloid peptides. Two processes (random/helix-to-beta-sheet and aggregation of beta-sheets) and multiple conformational states were observed before the most stable form was attained. beta-Amyloid peptides undergo decomposition in basic buffers containing Ca(2+); this process should be avoided during aging experiments.
Szabó
Z
Z
Department of Medical Chemistry, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Klement
E
E
Jost
K
K
Zarándi
M
M
Soós
K
K
Penke
B
B
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000592:standards*; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012015:Reference Standards; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
D016229:Amyloid beta-Peptides; D046911:Macromolecular Substances