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  • Title: Specific fluorescent detection of fibrillar alpha-synuclein using mono- and trimethine cyanine dyes.
    Author: Volkova KD, Kovalska VB, Balanda AO, Losytskyy MY, Golub AG, Vermeij RJ, Subramaniam V, Tolmachev OI, Yarmoluk SM.
    Journal: Bioorg Med Chem; 2008 Feb 01; 16(3):1452-9. PubMed ID: 17980608.
    Abstract:
    With the aim of searching of novel amyloid-specific fluorescent probes the ability of series of mono- and trimethine cyanines based on benzothiazole, pyridine and quinoline heterocycle end groups to recognize fibrillar formations of alpha-synuclein (ASN) was studied. For the first time it was revealed that monomethine cyanines can specifically increase their fluorescence in aggregated ASN presence. Dialkylamino-substituted monomethine cyanine T-284 and meso-ethyl-substituted trimethine cyanine SH-516 demonstrated the higher emission intensity and selectivity to aggregated ASN than classic amyloid stain Thioflavin T, and could be proposed as novel efficient fluorescent probes for fibrillar ASN detection. Studies of structure-function dependences have shown that incorporation of amino- or diethylamino- substituents into the 6-position of the benzothiazole heterocycle yields in a appearance of a selective fluorescent response to fibrillar alpha-synuclein presence. Performed calculations of molecular dimensions of studied cyanine dyes gave us the possibility to presume, that dyes bind with their long axes parallel to the fibril axis via insertion into the neat rows (so called 'channels') running along fibril.
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