RESUMEN

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.

Asunto(s)

Péptidos beta-Amiloides/antagonistas & inhibidores , Secuencia de Aminoácidos , Péptidos beta-Amiloides/química , Dicroismo Circular , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular