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.
Matharu
Balpreet
B
Neurodegeneration Unit, Basic Medical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. Balpreet@doctors.org.uk
El-Agnaf
Omar
O
Razvi
Amna
A
Austen
Brian M
BM
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010455:Peptides; C078592:amyloid beta-protein (1-40)