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Glycoconjugated metallohelices have improved nuclear delivery and suppress tumour growth in vivo.

Autoři: Song H., Allison S. J., Brabec V., Bridgewater H.E., Kasparkova J., Kostrhunova H., Novohradsky V., Phillips R.M., Pracharova J., Rogers N.J., Shepherd S.L., Scott P.Publikováno :  Angewandte Chemie International Edition 132(34), 14785-14793Rok: 2020

Monosaccharides are added to the hydrophilic face of a self‐assembled asymmetric Fe(II) metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water‐stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53+/+) with respect to the non‐cancerous ARPE‐19 cell line. While the most selective compound is a glucose‐appended enantiomer, its cellular entry is not mainly glucose transporter‐mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5‐fold, and a non‐destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d; performance as good as cisplatin but with the advantage of no weight loss in the subjects.


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