Development of retro-inverso peptides as anti-aggregation drugs for β-amyloid in Alzheimer's disease.

Alzheimer's disease (AD) is a devastating degenerative disorder of the brain for which there is no cure or effective treatment. There is much evidence to suggest that β-amyloid protein (Aβ) aggregation in the brain leading to deposits is an important step in the development of AD. Recently, two peptides, RGKLVFFGR (OR1) and RGKLVFFGR-NH(2) (OR2) containing the sequence KLVFF, which is the central region (residues 16-20) of Aβ, have been found to be potent inhibitors of Aβ aggregate formation. Here we report that retro-inversion of these sequences increases efficacy of the peptides in the inhibition of aggregation and toxicity of β-amyloid. We describe the synthesis and inhibitory properties of these retro-inverso peptides.