Specific fluorescent detection of fibrillar alpha-synuclein using mono- and trimethine cyanine dyes

Kateryna D Volkova, V B Kovalska, A O Balanda, M Yu Losytskyy, A G Golub, R J Vermeij, V Subramaniam, O I Tolmachev, S M Yarmoluk

    Research output: Contribution to JournalArticleAcademicpeer-review

    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.

    Original languageEnglish
    Pages (from-to)1452-9
    Number of pages8
    JournalBioorganic and Medicinal Chemistry
    Volume16
    Issue number3
    DOIs
    Publication statusPublished - 1 Feb 2008

    Keywords

    • Buffers
    • Carbocyanines
    • Fluorescent Dyes
    • Humans
    • Models, Molecular
    • Molecular Structure
    • Protein Binding
    • alpha-Synuclein
    • Journal Article

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