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Chiral metallohelices enantioselectively target hybrid human telomeric G-quadruplex DNA
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Zhao, Andong, Howson, Suzanne E., Zhao, Chuanqi, Ren, Jinsong, Scott, Peter, Wang, Chunyu and Qu, Xiaogang (2017) Chiral metallohelices enantioselectively target hybrid human telomeric G-quadruplex DNA. Nucleic Acids Research, 45 (9). pp. 5026-5035. doi:10.1093/nar/gkx244 ISSN 0305-1048.
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WRAP-chiral-metallohelices-enantioselectively-target-hybrid-Scott-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons: Attribution-Noncommercial 4.0. Download (2176Kb) | Preview |
Official URL: https://doi.org/10.1093/nar/gkx244
Abstract
The design and synthesis of metal complexes that can specifically target DNA secondary structure has attracted considerable attention. Chiral metallosupramolecular complexes (e.g. helicates) in particular display unique DNA-binding behavior, however until recently few examples which are both water-compatible and enantiomerically pure have been reported. Herein we report that one metallohelix enantiomer , available from a diastereoselective synthesis with no need for resolution, can enantioselectively stabilize human telomeric hybrid G-quadruplex and strongly inhibit telomerase activity with IC 50 of 600 nM. In contrast, no such a preference is observed for the mirror image complex . More intriguingly, neither of the two enantiomers binds specifically to human telomeric antiparallel G-quadruplex. To the best of our knowledge, this is the first example of one pair of enantiomers with contrasting selectivity for human telomeric hybrid G-quadruplex. Further studies show that can discriminate human telomeric G-quadruplex from other telomeric G-quadruplexes.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||
| SWORD Depositor: | Library Publications Router | ||||||||
| Library of Congress Subject Headings (LCSH): | Enantiomers, Chirality, Telomerase, Quadruplex nucleic acids | ||||||||
| Journal or Publication Title: | Nucleic Acids Research | ||||||||
| Publisher: | Oxford University Press | ||||||||
| ISSN: | 0305-1048 | ||||||||
| Official Date: | 19 May 2017 | ||||||||
| Dates: |
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| Volume: | 45 | ||||||||
| Number: | 9 | ||||||||
| Page Range: | pp. 5026-5035 | ||||||||
| DOI: | 10.1093/nar/gkx244 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Reuse Statement (publisher, data, author rights): | ** From PubMed via Jisc Publications Router. ** History: ** received: 22-12-2016 ** accepted: 30-03-2017 | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 19 October 2017 | ||||||||
| Date of first compliant Open Access: | 23 October 2017 | ||||||||
| Funder: | China. Guo jia ke xue ji shu bu [Ministry of Science and Technology] (CMST), Guo jia zi ran ke xue ji jin wei yuan hui (China) [National Natural Science Foundation of China] (NSFC) | ||||||||
| Grant number: | 2012CB720602 (CMST), 21210002, 21431007, 21533008, 21572216 (NSFC) |
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