TRIFLUOROACETIC-ACID PRETREATMENT REPRODUCIBLY DISAGGREGATES THE AMYLOID BETA-PEPTIDE

Major problems exist with pharmacological and biophysical studies of t he synthetic beta(1-42) peptide, in that the results often lack reprod ucibility. The starting aggregation states and structures of the vario us synthetic commercial lots appear to vary, resulting in significant lot-to-lot variability. We describe here an easy, efficient trifluoroa cetic acid (TFA) pretreatment method that renders the A beta easily so luble both in aqueous, buffered solutions and in organic solvents such as hexafluoroisopropanol (HFIP) or dimethylsulfoxide (DMSO). The TFA treated A beta exhibits the properties of monomeric, random coil struc tures and lacks pre-aggregated material that can act as seeds in fibri lization assays, thus reducing the batch to batch variation. In additi on, nuclear magnetic resonance (NMR) spectra recorded in deuterated TF A allow measurement of the peptide purity that is nor obtainable with other analytical methods.