Selective binding of zn(2+) complexes to human telomeric g-quadruplex DNA. Siters, K. E, Fountain, M. A, & Morrow, J. R Inorganic chemistry, 53(21):11540–51, November, 2014. ![Selective binding of zn(2+) complexes to human telomeric g-quadruplex DNA. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex The Zn(2+) complex of 5-(1,4,7,10-tetraazacyclododecan-1-ylsulfonyl)-N,N-dimethylnaphthalen-1-amine, Zn(DSC), binds selectively to the biologically relevant human telomeric (H-Telo) G-quadruplex. An increase in the Zn(DSC) dansyl group fluorescence with a simultaneous shift in emission is consistent with the complex binding to H-Telo. The H-Telo G-quadruplex has two binding sites for Zn(DSC) with binding constants in the low micromolar range (2.5 μM). Isothermal calorimetric titrations confirm low micromolar dissociation constants with a 2:1 stoichiometry. The interaction between H-Telo and Zn(DSC) is highly pH-dependent, consistent with binding to the unpaired thymines in the G-quadruplex loops. As a result, Zn(DSC) selectively binds to H-Telo over duplex DNA. In contrast to Zn(2+), Fe(2+) and Co(2+) do not complex to the DSC macrocycle appreciably under the conditions of the experiment. The Cu(2+) complex of DSC does not interact measurably with the H-Telo G-quadruplex. Interestingly, the H-Telo-Zn(DSC) adduct self-assembles from its individual components at physiological pH and 100 mM KCl. The self-assembly feature, which is specific for the Zn(2+) ion, suggests that this system may be viable as a Zn(2+) sensor. Pentanucleotides were studied in order to better describe the binding of Zn(DSC) to thymine sequences. NMR studies were consistent with the binding of Zn(DSC) to thymine-containing oligonucleotides including CCTCC, CTTCC, and CTCTC. Studies showed that the dansyl group of Zn(DSC) interacts with thymines in CTTCC. Fluorescence spectroscopy and ITC data indicate that Zn(DSC) forms 2:1 adducts with thymines that are spaced (CTCTC) but not tandem thymines (CTTCC). These data are consistent with one Zn(DSC) complex binding to two separate loops in the G-quadruplex. A second Zn(2+) complex containing an acridine pendent, Zn(ACR), binds tightly to pentanucleotides with both tandem and spaced thymines. Zn(ACR) indiscriminately binds to both H-Telo and duplex DNA.
@article{Siters2014,
title = {Selective binding of zn(2+) complexes to human telomeric g-quadruplex {DNA}.},
volume = {53},
issn = {1520-510X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25310175},
doi = {10.1021/ic501484p},
abstract = {The Zn(2+) complex of 5-(1,4,7,10-tetraazacyclododecan-1-ylsulfonyl)-N,N-dimethylnaphthalen-1-amine, Zn(DSC), binds selectively to the biologically relevant human telomeric (H-Telo) G-quadruplex. An increase in the Zn(DSC) dansyl group fluorescence with a simultaneous shift in emission is consistent with the complex binding to H-Telo. The H-Telo G-quadruplex has two binding sites for Zn(DSC) with binding constants in the low micromolar range (2.5 μM). Isothermal calorimetric titrations confirm low micromolar dissociation constants with a 2:1 stoichiometry. The interaction between H-Telo and Zn(DSC) is highly pH-dependent, consistent with binding to the unpaired thymines in the G-quadruplex loops. As a result, Zn(DSC) selectively binds to H-Telo over duplex DNA. In contrast to Zn(2+), Fe(2+) and Co(2+) do not complex to the DSC macrocycle appreciably under the conditions of the experiment. The Cu(2+) complex of DSC does not interact measurably with the H-Telo G-quadruplex. Interestingly, the H-Telo-Zn(DSC) adduct self-assembles from its individual components at physiological pH and 100 mM KCl. The self-assembly feature, which is specific for the Zn(2+) ion, suggests that this system may be viable as a Zn(2+) sensor. Pentanucleotides were studied in order to better describe the binding of Zn(DSC) to thymine sequences. NMR studies were consistent with the binding of Zn(DSC) to thymine-containing oligonucleotides including CCTCC, CTTCC, and CTCTC. Studies showed that the dansyl group of Zn(DSC) interacts with thymines in CTTCC. Fluorescence spectroscopy and ITC data indicate that Zn(DSC) forms 2:1 adducts with thymines that are spaced (CTCTC) but not tandem thymines (CTTCC). These data are consistent with one Zn(DSC) complex binding to two separate loops in the G-quadruplex. A second Zn(2+) complex containing an acridine pendent, Zn(ACR), binds tightly to pentanucleotides with both tandem and spaced thymines. Zn(ACR) indiscriminately binds to both H-Telo and duplex DNA.},
number = {21},
journal = {Inorganic chemistry},
author = {Siters, Kevin E and Fountain, Matthew A and Morrow, Janet R},
month = nov,
year = {2014},
pmid = {25310175},
keywords = {\#nosource},
pages = {11540--51},
}
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Isothermal calorimetric titrations confirm low micromolar dissociation constants with a 2:1 stoichiometry. The interaction between H-Telo and Zn(DSC) is highly pH-dependent, consistent with binding to the unpaired thymines in the G-quadruplex loops. As a result, Zn(DSC) selectively binds to H-Telo over duplex DNA. In contrast to Zn(2+), Fe(2+) and Co(2+) do not complex to the DSC macrocycle appreciably under the conditions of the experiment. The Cu(2+) complex of DSC does not interact measurably with the H-Telo G-quadruplex. Interestingly, the H-Telo-Zn(DSC) adduct self-assembles from its individual components at physiological pH and 100 mM KCl. The self-assembly feature, which is specific for the Zn(2+) ion, suggests that this system may be viable as a Zn(2+) sensor. Pentanucleotides were studied in order to better describe the binding of Zn(DSC) to thymine sequences. NMR studies were consistent with the binding of Zn(DSC) to thymine-containing oligonucleotides including CCTCC, CTTCC, and CTCTC. Studies showed that the dansyl group of Zn(DSC) interacts with thymines in CTTCC. Fluorescence spectroscopy and ITC data indicate that Zn(DSC) forms 2:1 adducts with thymines that are spaced (CTCTC) but not tandem thymines (CTTCC). These data are consistent with one Zn(DSC) complex binding to two separate loops in the G-quadruplex. A second Zn(2+) complex containing an acridine pendent, Zn(ACR), binds tightly to pentanucleotides with both tandem and spaced thymines. 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An increase in the Zn(DSC) dansyl group fluorescence with a simultaneous shift in emission is consistent with the complex binding to H-Telo. The H-Telo G-quadruplex has two binding sites for Zn(DSC) with binding constants in the low micromolar range (2.5 μM). Isothermal calorimetric titrations confirm low micromolar dissociation constants with a 2:1 stoichiometry. The interaction between H-Telo and Zn(DSC) is highly pH-dependent, consistent with binding to the unpaired thymines in the G-quadruplex loops. As a result, Zn(DSC) selectively binds to H-Telo over duplex DNA. In contrast to Zn(2+), Fe(2+) and Co(2+) do not complex to the DSC macrocycle appreciably under the conditions of the experiment. The Cu(2+) complex of DSC does not interact measurably with the H-Telo G-quadruplex. Interestingly, the H-Telo-Zn(DSC) adduct self-assembles from its individual components at physiological pH and 100 mM KCl. The self-assembly feature, which is specific for the Zn(2+) ion, suggests that this system may be viable as a Zn(2+) sensor. Pentanucleotides were studied in order to better describe the binding of Zn(DSC) to thymine sequences. NMR studies were consistent with the binding of Zn(DSC) to thymine-containing oligonucleotides including CCTCC, CTTCC, and CTCTC. Studies showed that the dansyl group of Zn(DSC) interacts with thymines in CTTCC. Fluorescence spectroscopy and ITC data indicate that Zn(DSC) forms 2:1 adducts with thymines that are spaced (CTCTC) but not tandem thymines (CTTCC). These data are consistent with one Zn(DSC) complex binding to two separate loops in the G-quadruplex. A second Zn(2+) complex containing an acridine pendent, Zn(ACR), binds tightly to pentanucleotides with both tandem and spaced thymines. 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