It seems likely that the beta -amyloid precursor protein (APP) and the pres
enilins (PS-1/2) play important roles in the development of Alzheimer's dis
ease (AD). Attempts to mimic the biochemical actions of these proteins are
often made by the application of fragments of these proteins. However, the
synthesis elf these segments by conventional methods of peptide synthesis i
s problematic. We have synthesized several C-terminal fragments of APP and
PS-1/2 by solid-phase synthesis through combination of automatic and manual
methods of synthesis. This permits solution of the 'difficult sequences' i
n the solid-phase synthesis of these peptides. Some details of the synthese
s of nine segments are presented in this paper. Copyright (C) 2001 European
Peptide Society and John Wiley & Sons, Ltd.