title: A peptide probe for detection of various beta-amyloid oligomers.
abstract: Aggregation of β-amyloid (Aβ) is implicated in the pathology of Alzheimer's disease (AD). A considerable amount of data has identified soluble Aβ oligomers as potentially significant toxic agents. Rapid, specific and quantitative detection is preferred for accurate profiling of structurally unstable Aβ oligomers as well as for implementation of high-throughput assays for pharmaceutical applications. PG46 is an engineered Aβ variant, constructed by integrating Aβ self-recognition sequences with the conformation-sensitive biarsenical fluorescent dye, FlAsH. PG46 was found to be an effective peptide probe, which detected Aβ oligomers specifically and quantitatively within one hour. However, PG46 was highly aggregation-prone and displayed a limited repertoire of detectable Aβ oligomers. Here, we report the creation of a novel molecular probe, PG44, by C-terminal truncation of PG46. PG44 exhibited a reduced self-aggregation propensity and a different conformation when compared to PG46, and generated specific FlAsH fluorescence signals as a result of binding to various Aβ oligomers, including those not readily detectable by PG46. We also show that sensitivity of PG44 for detection of certain Aβ oligomers may be increased by lowering PG44 concentration and thus decreasing the extent of self-aggregation of PG44. Our results suggest that PG44 can serve as an important molecular probe with a broadened repertoire of detectable Aβ oligomeric aggregates. We believe that detection of Aβ oligomers using our peptide probe would potentially contribute toward a better understanding of the molecular basis of Aβ oligomerization and the development of Aβ oligomer-based early diagnostics as well as therapeutic drugs targeting Aβ oligomers.
authors: Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, Brooklyn, NY 11201, USA. jkim@poly.edu
authors: Yang
authors: Y
authors: Hu
authors: Baihao
authors: B
authors: Su
authors: HeQiu
authors: H
authors: Zheng
authors: Jin Ryoun
authors: JR
authors: Kim
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D015335:Molecular Probes / Q000737:chemistry*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012996:Solutions; D013050:Spectrometry, Fluorescence
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D015335:Molecular Probes; D009842:Oligopeptides; D012996:Solutions