A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers

Yang Hu, Baihao Su, Chung Sei Kim, Michael Hernandez, Agueda Rostagno, Jorge Ghiso, Jin Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2409-2418
Number of pages10
JournalChemBioChem
Volume11
Issue number17
DOIs
StatePublished - Nov 2010

Fingerprint

Oligomers
Amyloid
Fluorescence
Amyloidogenic Proteins
Peptides
Preclinical Drug Evaluations
Poisons
Alzheimer Disease
Coloring Agents
Molecular Weight
Pathology
Oligomerization
Self assembly
Conformations
Screening
Agglomeration
Molecular weight
Pharmaceutical Preparations

Keywords

  • Aggregation
  • Amyloid beta-peptides
  • Oligomers
  • Protein engineering
  • Protein-protein interactions

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Hu, Y., Su, B., Kim, C. S., Hernandez, M., Rostagno, A., Ghiso, J., & Kim, J. (2010). A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers. ChemBioChem, 11(17), 2409-2418. https://doi.org/10.1002/cbic.201000435

A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers. / Hu, Yang; Su, Baihao; Kim, Chung Sei; Hernandez, Michael; Rostagno, Agueda; Ghiso, Jorge; Kim, Jin.

In: ChemBioChem, Vol. 11, No. 17, 11.2010, p. 2409-2418.

Research output: Contribution to journalArticle

Hu, Y, Su, B, Kim, CS, Hernandez, M, Rostagno, A, Ghiso, J & Kim, J 2010, 'A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers', ChemBioChem, vol. 11, no. 17, pp. 2409-2418. https://doi.org/10.1002/cbic.201000435
Hu Y, Su B, Kim CS, Hernandez M, Rostagno A, Ghiso J et al. A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers. ChemBioChem. 2010 Nov;11(17):2409-2418. https://doi.org/10.1002/cbic.201000435
Hu, Yang ; Su, Baihao ; Kim, Chung Sei ; Hernandez, Michael ; Rostagno, Agueda ; Ghiso, Jorge ; Kim, Jin. / A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers. In: ChemBioChem. 2010 ; Vol. 11, No. 17. pp. 2409-2418.
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