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Chiral metallohelices enantioselectively target hybrid human telomeric G-quadruplex DNA.

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 Δ1a, available from a diastereoselective synthesis with no need for resolution, can enantioselectively stabilize human telomeric hybrid G-quadruplex and strongly inhibit telomerase activity with IC50 of 600 nM. In contrast, no such a preference is observed for the mirror image complex Λ1a. 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 Δ1a can discriminate human telomeric G-quadruplex from other telomeric G-quadruplexes.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Zhao A,Howson SE,Zhao C,Ren J,Scott P,Wang C,Qu X

doi

10.1093/nar/gkx244

subject

Has Abstract

pub_date

2017-05-19 00:00:00

pages

5026-5035

issue

9

eissn

0305-1048

issn

1362-4962

pii

3294593

journal_volume

45

pub_type

杂志文章

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