Identification of peptides that specifically bind Abeta1-40 amyloid in vitro and amyloid plaques in Alzheimer's disease brain using phage display.
The accumulation of the amyloid-beta (Abeta) peptides in amyloid plaques correlates with pathologic changes that occur in the brains of patients with Alzheimer's disease (AD). The ability to directly target reagents to the amyloid form of the Abeta peptide may allow the delivery of neuroprotective agents to make amyloid plaques less toxic, the delivery of amyloid-destroying molecules to eliminate plaques, or the delivery of reagents to prevent amyloid plaque formation. In addition, such reagents may be useful as diagnostic tools to quantitate the extent of amyloid plaque formation in AD patients. As a step toward these goals, we have used phage peptide display technology to identify peptides that bind specifically to the amyloid form of the Abeta(1-40) peptide. Here we identify two 20-amino acid peptides with similar structural features that bind to the amyloid form of Abeta(1-40) but not to monomeric Abeta(1-40). A recombinant form of one of these peptides was produced in Escherichia coli as a fusion protein with thioredoxin. After purification, this reagent bound Abeta(1-40) amyloid in vitro with a K(d) of 60 nM and specifically labeled amyloid plaques in AD brains. A chemically synthesized version of this peptide also bound Abeta(1-40) amyloid and specifically stained amyloid plaques in AD brain. These peptide sequences represent new potential carrier molecules to deliver medicines to amyloid plaques in AD patients and to image plaques in AD brains.
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D020539:Sequence Analysis, Protein / Q000379:methods
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019151:Peptide Library; C078592:amyloid beta-protein (1-40)