EFFECT OF HYDROPHILIC AMINO-ACID SUBSTITUTIONS ON THE SOLUBILITY AND SECONDARY STRUCTURE OF BETA-A(1-42)

Modified sequences of the amyloid peptide beta A(1-42) and its shorter Phe-sulfonic acid derivatives with enhanced solubility in aqueous sol utions were synthesized, and the conformational consequences were stud ied by comparative circular dichroism and Fourier transform infrared s pectroscopy. Measurements were performed in trifluoroethanol/water mix tures and aqueous octyl-glucoside solutions. Replacement of the hydrop hobic amino acids by less hydrophobic and hydrophilic residues resulte d in a predominantly random conformation of the modified amyloid pepti des in water, while beta A(1-42) exhibited 55% beta-sheet structure. I n the helix-promoting solvent trifluoroethanol the com pletely dissolv ed peptides are present mostly in an alpha-helical conformation. In oc tyl glucoside solution--at and above the critical micelle concentratio n--beta A(1-42) has higher beta-sheet content (82%), contrary to the m ore hydrophilic modified peptides which retain a predominant random co nformation irrespective of the absence or presence of the micelles. Ou r data suggest that the amide groups of the backbone and/or the polar sidechain functions of beta A(1-42) interact with the glucose surface of micelles possibly mainly by H-bonds creating a beta-sheet forming c ore which then facilitates intersheet stacking. The modified peptides do not bind to the surface of micelles or their binding has no beta-or dering effect on the peptide chains. (C) 1996 John Wiley & Sons, Inc.