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1: J Am Chem Soc. 2006 Nov 15;128(45):14456-7.Click here to read Links

Inhibition of beta-amyloid fibrillization by directed evolution of a beta-sheet presenting miniature protein.

Smith TJ, Stains CI, Meyer SC, Ghosh I.

Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.

We describe the directed evolution of a miniature beta-sheet protein for targeting beta-amyloid oligomers implicated in Alzheimer's disease. Circular dichroism spectroscopy, thermal denaturation experiments, and immunoglobulin binding assays established that our beta-amyloid-targeted miniature protein, TJ10, presents a well-folded thermostable beta-sheet. TJ10 was found to prevent beta-amyloid fibrillization at stoichiometric concentrations and was also an effective inhibitor at substoichiometric concentrations. Thus our results provide a new and potent beta-sheet chemical template for effectively targeting beta-amyloid while also demonstrating a general strategy for targeting proteins implicated in other amyloidogenic diseases.

PMID: 17090018 [PubMed - indexed for MEDLINE]