Allosteric cross-talk in chromatin can mediate drug-drug synergy

Journal: Nature Communications

Published: 2017-03-30

DOI: 10.1038/ncomms14860

Affiliations: 3

Authors: 8

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Research Highlight

Off-site workers prove effective

© Photography by ZhangXun/Moment/Getty

© Photography by ZhangXun/Moment/Getty

The binding of an anticancer agent to the proteins that spool around DNA helps an unrelated drug — one used to treat rheumatoid arthritis — to bind more efficiently in cancer cells.

Together, the two drugs kill many more ovarian cancer cells than either agent alone.

A team co-led by researchers at Nanyang Technological University showed that the therapeutic synergy results from a ‘domino’ model of drug attachment to the histone proteins that package DNA. After the anticancer drug RAPTA-T binds the DNA, it changes the shape of the histone in a way that makes it easier for the antirheumatic agent auranofin to bind at a distant site, different to the one where it normally acts.

While this kind of ‘off-site’ activity often leads to problematic side effects, in this case, it enhances the drugs’ destructive power against tumours.

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  1. Nature Communications 8, 14860 (2017). doi: 10.1038/ncomms14860
Institutions FC WFC
EPFL Institute of Chemical Sciences and Engineering (ISIC), Switzerland 0.50 0.50
School of Biological Sciences (SBS), NTU, Singapore 0.44 0.44
NTU Institute of Structural Biology (NISB), Singapore 0.06 0.06