Improved preparation of β-amyloid(1–43): structural insight leading to optimised positioning of N-(2-hydroxy-4-methoxybenzyl)(Hmb) backbone amide protection

Abstract

We report an improved synthetic strategy for the preparation of the amyloidogenic protein fragment β-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 phenylalanine²⁰, was determined from a β-hairpin model derived for the C-terminal region of the resin-bound peptide. This improved scheme provides the final product in 28% overall yield.