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Chemical probes that selectively recognize the earliest A? oligomers in complex mixtures.

ABSTRACT: Alzheimer's disease (AD) is characterized by the self-assembly of amyloid beta (A?) peptides. Recent models implicate some of the earliest A? oligomers, such as trimers and tetramers, in disease. However, the roles of these structures remain uncertain, in part, because selective probes of their formation are not available. Toward that goal, we generated bivalent versions of the known A? ligand, the pentapeptide KLVFF. We found that compounds containing sufficiently long linkers (?19 to 24 Å) recognized primarily A? trimers and tetramers, with little binding to either monomer or higher order structures. These compounds might be useful probes for early A? oligomers.

SUBMITTER: Reinke AA

PROVIDER: S-EPMC3005376 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Chemical probes that selectively recognize the earliest Aβ oligomers in complex mixtures.

Reinke Ashley A AA Ung Peter M U PM Quintero Jerome J JJ Carlson Heather A HA Gestwicki Jason E JE

Journal of the American Chemical Society 20101124 50

Alzheimer's disease (AD) is characterized by the self-assembly of amyloid beta (Aβ) peptides. Recent models implicate some of the earliest Aβ oligomers, such as trimers and tetramers, in disease. However, the roles of these structures remain uncertain, in part, because selective probes of their formation are not available. Toward that goal, we generated bivalent versions of the known Aβ ligand, the pentapeptide KLVFF. We found that compounds containing sufficiently long linkers (∼19 to 24 Å) rec ...[more]

PMID: 21105683

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Project description:With burgeoning population and diminishing availability of freshwater resources, the world continues to expand the use of alternative water resources for drinking, and the quality of these sources has been a great concern for the public as well as public health professionals. In vitro bioassays are increasingly being used to enable rapid, relatively inexpensive toxicity screening that can be used in conjunction with analytical chemistry data to evaluate water quality and the effectiveness of water treatment. In this study, a comprehensive bioassay battery consisting of 36 bioassays covering 18 biological endpoints was applied to screen the bioactivity of waters of varying qualities with parallel treatments. Samples include wastewater effluent, ultraviolet light (UV) and/or ozone advanced oxidation processed (AOP) recycled water, and infiltrated recycled groundwater. Based on assay sensitivity and detection frequency in the samples, several endpoints were highlighted in the battery, including assays for genotoxicity, mutagenicity, estrogenic activity, glucocorticoid activity, arylhydrocarbon receptor activity, oxidative stress response, and cytotoxicity. Attenuation of bioactivity was found to be dependent on the treatment process and bioassay endpoint. For instance, ozone technology significantly removed oxidative stress activity, while UV based technologies were most efficient for the attenuation of glucocorticoid activity. Chlorination partially attenuated genotoxicity and greatly decreased herbicidal activity, while groundwater infiltration efficiently attenuated most of the evaluated bioactivity with the exception of genotoxicity. In some cases, bioactivity (e.g., mutagenicity, genotoxicity, and arylhydrocarbon receptor) increased following water treatment, indicating that transformation products of water treatment may be a concern. Furthermore, several types of bioassays with the same endpoint were compared in this study, which could help guide the selection of optimized methods in future studies. Overall, this research indicates that a battery of bioassays can be used to support decision-making on the application of advanced water treatment processes for removal of bioactivity.

Dataset Information

Chemical probes that selectively recognize the earliest A? oligomers in complex mixtures.

Publications

Chemical probes that selectively recognize the earliest Aβ oligomers in complex mixtures.

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