IMPROVED PREPARATION OF BETA-AMYLOID(1-43) - STRUCTURAL INSIGHT LEADING TO OPTIMIZED POSITIONING OF N-(2-HYDROXY-4-METHOXYBENZYL) (HMB) BACKBONE AMIDE PROTECTION

We report an improved synthetic strategy for the preparation of the amyloidogenic protein fragment beta-amyloid(1-43). The scheme is based upon the generation of highly soluble N-(2-hydroxy-4-methoxybenzyl) (Hmb) backbone amide-protected intermediates. Optimal positioning of backbone protection at glycines(25,29,33,37) together with phenylalanine(20), was determined from a beta-hairpin model derived for the C-terminal region of the resin-bound peptide. This improved scheme provides the final product in 28% overall yield.