A peptide hairpin inhibitor of amyloid beta-protein oligomerization and fibrillogenesis.
Amyloid beta-protein (Abeta) self-assembly is linked strongly to Alzheimer's disease. We found that PP-Leu, a tridecapeptide analogue of broad-spectrum antiviral peptides termed theta-defensins, potently inhibits Abeta oligomer and fibril formation. This effect appeared to be mediated through sequestration of the amyloidogenic Abeta peptide in colloid-like assemblies. PP-Leu comprises a turn formed by a d-Pro-l-Pro amino acid dyad and stabilized by a disulfide bond, a motif that was exceptionally resistant to endoproteinase K digestion. This combination of assembly inhibitory activity and protease resistance suggests that PP-Leu may have potential therapeutic value.
Yamin
Ghiam
G
Medical Scientist Training Program, David Geffen School of Medicineat UCLA, USA.
Ruchala
Piotr
P
Teplow
David B
DB
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D010450:Endopeptidases / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects
D000682:Amyloid; D016229:Amyloid beta-Peptides; D004151:Dipeptides; D004220:Disulfides; D010455:Peptides; C448039:prolyl-proline; D010450:Endopeptidases; D007930:Leucine