title: 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.
authors.affiliation: Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.|University of Chinese Academy of Science, Beijing 100039, China.
authors.forename: Andong
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Howson
authors.affiliation: Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Scott
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, Jilin University, 2699 Qianjin Avenue, Changchun 130012, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Qu
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000737:chemistry; D007536:Isomerism; D008670:Metals / Q000737:chemistry*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D008670:Metals; D004247:DNA; D007501:Iron; D019098:Telomerase