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

Medical Scientist Training Program, David Geffen School of Medicineat UCLA, USA.
Biochemistry (Impact Factor: 3.02). 10/2009; 48(48):11329-31. DOI: 10.1021/bi901325g
Source: PubMed


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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Available from: Piotr Ruchala, Apr 09, 2015
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    • "(C) ThT monitoring of 10 μM Aβ aggregation and inhibitory effects of 100 μM peptides present from the beginning of the aggregation at 37°C. Inhibition values were taken at 12 hr due the decay in ThT fluorescence, particularly for uninhibited samples, which has been described elsewhere (Yamin et al., 2009). (D) Aβ toxicity after 6 hr of aggregation, as probed using the MTT assay and the SH-SY5Y cell line. "
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    • "homoserine O-methyl ether, Mes methanesulfonyl group, Nle norleucine, Nva norvaline, Ser Me serine O-methyl ether, Thr Me threonine O-methyl ether, Tle tert-Leucine, PEG 5 21-amino-4,7,10,13,16,19-hexaoxaheneicosanoic acid synthesis, (3) overall low cost of production, and (4) previously reported significant resistance to enzymatic degradation (Yamin et al. 2009). As an outcome, a new library of second generation DpVs (DpVs 2G , analogues DpV1601- 1632) was created. "
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