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A Strategy for Designing a Peptide Probe for Detection of β‐Amyloid Oligomers
Author(s) -
Hu Yang,
Su Baihao,
Kim ChungSei,
Hernandez Michael,
Rostagno Agueda,
Ghiso Jorge,
Kim Jin Ryoun
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000435
Subject(s) - oligomer , peptide , amyloid (mycology) , fluorescence , chemistry , biophysics , amyloid β , amyloid disease , protein aggregation , amyloid fibril , drug development , biochemistry , combinatorial chemistry , biology , drug , disease , medicine , organic chemistry , inorganic chemistry , physics , pathology , quantum mechanics , pharmacology
Aggregation of β‐amyloid (Aβ) is implicated in the pathology of Alzheimer's disease. Development of a robust strategy to detect Aβ oligomeric intermediates, which have been identified as significant toxic agents, would be highly beneficial in the screening of drug candidates as well as enhancing our understanding of Aβ oligomerization. Rapid, specific and quantitative detection, currently unavailable, would be highly preferred for accurate and reliable probing of transient Aβ oligomers. Here, we report the development of a novel peptide probe, PG46, based on the nature of Aβ self‐assembly and the conformation‐sensitive fluorescence of the biarsenical dye, FlAsH. PG46 was found to bind to Aβ oligomers and displayed an increase in FlAsH fluorescence upon binding. No such event was observed when PG46 was co‐incubated with Aβ low‐molecular‐weight species or Aβ fibrils. Aβ oligomer detection was fast, and occurred within one hour without any additional sample incubation or preparation. We anticipate that the development of a strategy for detection of amyloid oligomers described in this study will be directly relevant to a host of other amyloidogenic proteins.