Inhibition of beta-amyloid aggregation and neurotoxicity by complementary (antisense) peptides.

Complementary peptides are coded for by the nucleotide sequence (read 5'-->3') of the complementary strand of DNA. By reading the sequence of complementary DNA in the 3'-->5' direction, alternative complementary peptides may be derived. We describe the derivation, testing and analysis of six complementary peptides designed against beta-amyloid peptide 1-40 (Abeta, 40). Data is presented to show that one peptide, designated 3' -->5' betaCP1-15, binds specifically to Abeta 1-40, and inhibits both fibrilisation and neurotoxicity in vitro. This suggests that complementary peptides could be useful leads for drug discovery, especially where diseases of protein misfolding are concerned.