Design strategies for anti-amyloid agents.
Numerous diseases have been linked to a common pathogenic process called amyloidosis, whereby proteins or peptides clump together in the brain or body to form toxic soluble oligomers and/or insoluble fibres. An attractive strategy to develop therapies for these diseases is therefore to inhibit or reverse protein/peptide aggregation. A diverse range of small organic ligands have been found to act as aggregation inhibitors. Alternatively, the wild-type peptide can be derivatised so that it still binds to the amyloid target, but prevents further aggregation. This can be achieved by adding a bulky group or charged amino acid to either end of the peptide, or by incorporating proline residues or N-methylated amide groups.
Mason
Jody M
JM
Department of Biomolecular Sciences, UMIST, PO Box 88, Manchester M60 1QD, UK.
Kokkoni
Nicoleta
N
Stott
Kelvin
K
Doig
Andrew J
AJ
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding
D016229:Amyloid beta-Peptides; D010455:Peptides