Aggregation of beta-amyloid (Abeta) is implicated in the pathology of Alzheimer’s disease (AD). Development of a robust strategy to detect Abeta oligomeric intermediates, identified as significant toxic agents, would be highly beneficial in the screening of drug candidates as well as enhancing our understanding of Abeta oligomerization. Rapid, specific and quantitative detection, currently unavailable, would be highly preferred for accurate and reliable probing of transient Abeta oligomers. We have previously reported the development of a peptide probe, PG46, for rapid, specific and quantitative detection of Abeta oligomers. PG46 was created by combining Abeta binding sequences and a conformation-sensitive fluorescence dye, FlAsH.
In this presentation, we will report the creation of a second generation of peptide probes by modifying the sequence of PG46. These new peptide probes displayed different conformations compared to PG46, and exhibited novel specificity toward certain Abeta oligomeric forms, which were not recognizable by PG46. These novel peptide probes generated fluorescence signals upon binding to Abeta oligomers through an increase in the quantum yield of bound FlAsH. We anticipate that our peptide probes for Abeta oligomer detection will benefit the understanding of Abeta oligomerization determinants, AD diagnostics and drug development.
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