Aggregation of Aβ(1-42) in the presence of short peptides:: conformational studies

CID and infrared spectroscopic studies were performed on (i) the inhibitory effects of equimolar quantities of LPFFD-OH and LPYFD-NH2 on the time-dependent aggregation of amyloid beta-protein (A beta) (1-42) and (ii) the beta-sheet-breaker effects of two-fold molar excess of the pentapeptides on aggregated A beta(1-42) aged 1 week. The data obtained from the time-dependent studies demonstrated that LPFFD-OH did not significantly influence, whereas LPYFD-NH2 exerted some inhibitory effect on the aggregation of A beta(1-42). When added to a solution of A beta(1-42) aged 1 week, LPFFD-OH accelerated, while LPYFD-NH2 delayed, but did not prevent further fibrillogenesis. The difference in the effects of these two pentapeptides on the aggregational profile of A beta(1-42) is probably due to the difference in their conformational preferences: LPFFD-OH adopts a beta-turn and extended structures, while LPYFD-NH2 adopts a prevailing beta-turn conformation. Copyright (C) 2008 European Peptide Society and John Wiley & Sons, Ltd.