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Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo
Author(s) -
Song Hualong,
Allison Simon J.,
Brabec Viktor,
Bridgewater Hannah E.,
Kasparkova Jana,
Kostrhunova Hana,
Novohradsky Vojtech,
Phillips Roger M.,
Pracharova Jitka,
Rogers Nicola J.,
Shepherd Samantha L.,
Scott Peter
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202006814
Subject(s) - monosaccharide , chemistry , in vivo , supramolecular chemistry , cisplatin , biophysics , selectivity , conjugated system , dna , glucose transporter , growth inhibition , enantiomer , cell growth , cell culture , combinatorial chemistry , biochemistry , stereochemistry , organic chemistry , insulin , molecule , biology , genetics , polymer , microbiology and biotechnology , chemotherapy , endocrinology , catalysis
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.