An FT-IR study of the beta-amyloid conformation: Standardization of aggregation grade

The aggregation of B-amyloid peptides is very important for their neurotoxi c effect; standardization of the aggregation grade is necessary for biologi cal experiments. Measurement of aggregation with physicochemical methods is a difficult task. The present work revealed that FT-IR can be used for stu dying the aggregation properties of beta-amyloid peptides and the effects o f environmental variables (solvent, pH, ions, and temperature) on aggregati on. In dimethyl sulfoxide or hexafluoroisopropanol, amyloid peptides are in a monomeric state; on dilution with phosphate buffer just before measureme nt is made, aggregation begins. A detailed two-dimensional FT-IR correlatio n spectroscopic study was made of the conformational transitions that occur during the aggregation of beta-amyloid peptides. Two processes (random/hel ix-to-beta-sheet and aggregation of beta-sheets) and multiple conformationa l states were observed before the most stable form was attained. beta-Amylo id peptides undergo decomposition in basic buffers containing Ca2+; this pr ocess should be avoided during aging experiments, (C) 1999 Academic Press.