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.
Heal
Jonathan R
JR
Imperial College Genetic Therapies Centre Department of Chemistry, Flowers Building, Armstrong Road Imperial College of Science, Technology and Medicine South Kensington, London, SW72AZ, UK.
Roberts
Gareth W
GW
Christie
Gary
G
Miller
Andrew D
AD
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity*; D016375:Antisense Elements (Genetics) / Q000737:chemistry / Q000494:pharmacology*; D015374:Biosensing Techniques; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000633:toxicity
D016229:Amyloid beta-Peptides; D016375:Antisense Elements (Genetics); D009498:Neurotoxins; D004247:DNA