Journal
BIOCHEMISTRY
Volume 48, Issue 48, Pages 11329-11331Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi901325g
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Funding
- UCLA Chemistry-Biology Interface program
- Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA
- Adams and Burnham endowments
- National Institutes of Health [AG027818]
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Amylold beta-protein (A beta) 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 A beta oligomer and fibril Formation. This effect appeared to be mediated through sequestration of the amyloidogenic A beta 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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