Article

A Peptide Hairpin Inhibitor of Amyloid beta-Protein Oligomerization and Fibrillogenesis

Medical Scientist Training Program, David Geffen School of Medicineat UCLA, USA.
Biochemistry (Impact Factor: 3.19). 10/2009; 48(48):11329-31. DOI: 10.1021/bi901325g
Source: PubMed

ABSTRACT 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.

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