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

Thaddeus J. Smith, Cliff I. Stains, Scott C. Meyer, Indraneel Ghosh

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)14456-14457
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number45
DOIs
StatePublished - Nov 15 2006

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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