The A beta 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater beta-sheet forming and aggregation propensities in vitro than full-length A beta

A beta isolared from neuritic plaque and vascular walls of the brains of pa tients with Alzheimer's disease has been shown to contain significant quant ities of A beta peptides which begin at residue (3)Glu or (11)Glu in the fo rm of pyroglutamyl residues (A beta 3pE and A beta 11pE). To investigate th e effects of these N-terminal modifications on the biophysical properties o f A beta, peptides A beta 1-40, A beta 3pE-40, A beta 11pE40, A beta 1-28, A beta 3pE-28, and A beta 11pE-28 were synthesized. Using circular dichrois m spectroscopy, we determined that the pyroglutamyl-containing peptides for m beta-sheet structure more readily than the corresponding full-length A be ta peptides, both in aqueous solutions and in 10% sodium dodecyl sulfate mi celles. Trifluoroethanol spectra indicated that the relative beta-sheet to alpha-helical stability is higher for the pyroglutamyl-containing peptides. Sedimentation experiments show that the pyroglutamyl-containing peptides h ave greater aggregation propensities than the corresponding full-length pep tides. Comparison between the A beta 40 and the A beta 28 series indicated that the greater beta-sheet forming and aggregation propensities of the pyr oglutamyl peptides are not simply due to an increase in hydrophobicity.