Glycerol-Based Contrast Agents: A Novel Series of Dendronized Pentamethine Dyes

  • The synthesis of water-soluble dyes, which absorb and emit in the range between 650 and 950 nm and display high extinction coefficients (ε) as well as high fluorescence quantum yields (Φf), is still a demand for optical imaging. We now present a synthetic route for the preparation of a new group of glycerol-substituted cyanine dyes from dendronized indole precursors that have been functionalized as Nhydroxysuccinimide (NHS) esters. High Φf values of up to 0.15 and extinction coefficients of up to 189 000 L mol−1 cm−1 were obtained for the pure dyes. Furthermore, conjugates of the new dendronized dyes with the antibody cetuximab (ctx) that were directed against the epidermal growth factor receptor (EGFR) of tumor cells could be prepared with dye to protein ratios between 0.3 and 2.2 to assess their potential as imaging probes. For the first time, ctx conjugates could be achieved without showing a decrease in Φf and with an increasing labeling degree that exceeded the value of the pureThe synthesis of water-soluble dyes, which absorb and emit in the range between 650 and 950 nm and display high extinction coefficients (ε) as well as high fluorescence quantum yields (Φf), is still a demand for optical imaging. We now present a synthetic route for the preparation of a new group of glycerol-substituted cyanine dyes from dendronized indole precursors that have been functionalized as Nhydroxysuccinimide (NHS) esters. High Φf values of up to 0.15 and extinction coefficients of up to 189 000 L mol−1 cm−1 were obtained for the pure dyes. Furthermore, conjugates of the new dendronized dyes with the antibody cetuximab (ctx) that were directed against the epidermal growth factor receptor (EGFR) of tumor cells could be prepared with dye to protein ratios between 0.3 and 2.2 to assess their potential as imaging probes. For the first time, ctx conjugates could be achieved without showing a decrease in Φf and with an increasing labeling degree that exceeded the value of the pure dye even at a labeling degree above 2. The incorporation of hydrophilically and sterically demanding dendrimers into cyanines prevented dimer formation after covalent conjugation to the antibody. The binding functionality of the resulting ctx conjugates to the EGFR was successfully demonstrated by cell microscopy studies using EGFR expressing cell lines. In summary, the combination of hydrophilic glycerol dendrons with reactive dye labels has been established for the first time and is a promising Approach toward more powerful fluorescent labels with less dimerization.zeige mehrzeige weniger

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Autor*innen:Jutta Pauli, V. Wycisk, P. Welker, A. Justies, Ute Resch-GengerORCiD, R. Haag, K. Licha
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):Bioconjugate Chemistry
Jahr der Erstveröffentlichung:2015
Verlag:ACS Publications
Verlagsort:Washington
Jahrgang/Band:26
Erste Seite:773
Letzte Seite:781
DDC-Klassifikation:Naturwissenschaften und Mathematik / Chemie / Analytische Chemie
Freie Schlagwörter:Contrast agent; Dye; Extinction coefficient; Fluorescence; Quantum yield
DOI:10.1021/acs.bioconjchem.5b00097
ISSN:1043-1802
Verfügbarkeit des Dokuments:Datei im Netzwerk der BAM verfügbar ("Closed Access")
Datum der Freischaltung:04.01.2017
Referierte Publikation:Nein
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