| Dihydroxybenzoic Acid Isomers Differentially Dissociate Soluble Biotinyl-Aβ(1-42) Oligomers. | |
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MedLine Citation:
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PMID: 22129351 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Polyphenolic compounds including a number of natural products such as resveretrol, curcumin, catechin derivatives, and nordihydroguaiaretic acid have effects on the assembly of Aβ fibrils and oligomers as well as on fibril morphology. Based on a lead structure obtained from a screen of a small molecule diversity library, simple benzoic acid derivatives distinguished by the number and position of hydroxyls on the aromatic ring displayed different abilities to dissociate pre-formed biotinyl-Aβ(1-42) oligomers. The 2, 3-, 2, 5-, and 3, 4- dihydroxybenzoic acid (DHBA) isomers were active oligomer dissociators. The remaining DHBA isomers and the monohydroxy and unsubstituted benzoic acids were inactive and did not compete with the active compounds to block oligomer dissociation. None of the compounds blocked oligomer assembly, indicating that they do not interact with monomeric Aβ to shift the oligomer-monomer equilibrium. Dissociating activity was not associated with quinone redox cycling capacity of the compounds. Gallic acid (3, 4, 5-trihydroxybenzoic acid) stabilized biotinyl-Aβ(1-42) oligomers against intrinsic dissociation and blocked the effects of the active dissociators, independent of the concentration of dissociator. A model for the mechanism of action of the DHBA dissociators proposes that these compounds destabilize oligomer structure promoting progressive monomer dissociation rather than fissioning oligomers into smaller, but still macromolecular species. Gallic acid blocks dissociation by stabilizing oligomers against this process. |
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Authors:
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Harry Levine; Levi M Lampe; Lina G Abdelmoti; Corinne Elizabeth Augelli-Szafran |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-30 |
Journal Detail:
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Title: Biochemistry Volume: - ISSN: 1520-4995 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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