Effect of hydrophilic amino acid substitutions on the solubility and secondary structure of βA (1-42)

Abstract

Modified sequences of the amyloid peptide βA (1–42) and its shorter Phe-sulfonic acid derivatives with enhanced solubility in aqueous solutions were synthesized, and the conformational consequences were studied by comparative circular dichroism and Fourier transform infrared spectroscopy. Measurements were performed in trifluoroethanol/water mixtures and aqueous octyl-glucoside solutions. Replacement of the hydrophobic amino acids by less hydrophobic and hydrophilic residues resulted in a predominantly random conformation of the modified amyloid peptides in water, while βA (1–42) exhibited 55% β-sheet structure. In the helix-promoting solvent trifluoroethanol the completely dissolved peptides are present mostly in an α-helical conformation. In octyl glucoside solution—at and above the critical micelle concentration—βA (1–42) has higher β-sheet content (82%), contrary to the more hydrophilic modified peptides which retain a predominant random conformation irrespective of the absence or presence of the micelles. Our data suggest that the amide groups of the backbone and/or the polar side-chain functions of βA (1–42) interact with the glucose surface of micelles possibly mainly by H-bonds creating a β-sheet forming core which then facilitates intersheet stacking. The modified peptides do not bind to the surface of micelles or their binding has no β-ordering effect on the peptide chains. © 1996 John Wiley & Sons, Inc.