Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo. 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. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 59(34):14677–14685, August, 2020. doi abstract bibtex 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.
@article{song_glycoconjugated_2020,
title = {Glycoconjugated {Metallohelices} have {Improved} {Nuclear} {Delivery} and {Suppress} {Tumour} {Growth} {In} {Vivo}},
volume = {59},
issn = {1433-7851},
doi = {10.1002/anie.202006814},
abstract = {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.},
number = {34},
urldate = {2020-07-07},
journal = {ANGEWANDTE CHEMIE-INTERNATIONAL EDITION},
author = {Song, Hualong and Allison, Simon J. and Brabec, Viktor and Bridgewater, Hannah E. and Kasparkova, Jana and Kostrhunova, Hana and Novohradsky, Vojtech and Phillips, Roger M. and Pracharova, Jitka and Rogers, Nicola J. and Shepherd, Samantha L. and Scott, Peter},
month = aug,
year = {2020},
pages = {14677--14685},
}
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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.","number":"34","urldate":"2020-07-07","journal":"ANGEWANDTE CHEMIE-INTERNATIONAL EDITION","author":[{"propositions":[],"lastnames":["Song"],"firstnames":["Hualong"],"suffixes":[]},{"propositions":[],"lastnames":["Allison"],"firstnames":["Simon","J."],"suffixes":[]},{"propositions":[],"lastnames":["Brabec"],"firstnames":["Viktor"],"suffixes":[]},{"propositions":[],"lastnames":["Bridgewater"],"firstnames":["Hannah","E."],"suffixes":[]},{"propositions":[],"lastnames":["Kasparkova"],"firstnames":["Jana"],"suffixes":[]},{"propositions":[],"lastnames":["Kostrhunova"],"firstnames":["Hana"],"suffixes":[]},{"propositions":[],"lastnames":["Novohradsky"],"firstnames":["Vojtech"],"suffixes":[]},{"propositions":[],"lastnames":["Phillips"],"firstnames":["Roger","M."],"suffixes":[]},{"propositions":[],"lastnames":["Pracharova"],"firstnames":["Jitka"],"suffixes":[]},{"propositions":[],"lastnames":["Rogers"],"firstnames":["Nicola","J."],"suffixes":[]},{"propositions":[],"lastnames":["Shepherd"],"firstnames":["Samantha","L."],"suffixes":[]},{"propositions":[],"lastnames":["Scott"],"firstnames":["Peter"],"suffixes":[]}],"month":"August","year":"2020","pages":"14677–14685","bibtex":"@article{song_glycoconjugated_2020,\n\ttitle = {Glycoconjugated {Metallohelices} have {Improved} {Nuclear} {Delivery} and {Suppress} {Tumour} {Growth} {In} {Vivo}},\n\tvolume = {59},\n\tissn = {1433-7851},\n\tdoi = {10.1002/anie.202006814},\n\tabstract = {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. 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