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Chiral metallo-supramolecular complexes selectively recognize human telomeric G-quadruplex DNA.

Yu H, Wang X, Fu M, Ren J, Qu X - Nucleic Acids Res. (2008)

Bottom Line: The chiral supramolecular complex has both small molecular chemical features and the large size of a zinc-finger-like DNA-binding motif.The complex is also convenient to synthesize and separate enantiomers.These results provide new insights into the development of chiral anticancer agents for targeting G-quadruplex DNA.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Inorganic Chemistry, Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

ABSTRACT
Here, we report the first example that one enantiomer of a supramolecular cylinder can selectively stabilize human telomeric G-quadruplex DNA. The P-enantiomer of this cylinder has a strong preference for G-quadruplex over duplex DNA and, in the presence of sodium, can convert G-quadruplexes from an antiparallel to a hybrid structure. The compound's chiral selectivity and its ability to discriminate quadruplex DNA have been studied by DNA melting, circular dichroism, gel electrophoresis, fluorescence spectroscopy and S1 nuclease cleavage. The chiral supramolecular complex has both small molecular chemical features and the large size of a zinc-finger-like DNA-binding motif. The complex is also convenient to synthesize and separate enantiomers. These results provide new insights into the development of chiral anticancer agents for targeting G-quadruplex DNA.

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Plot of DNA stabilization temperature versus the concentration of [Ni2L3]4+-P (filled symbols) or [Ni2L3]4+-M (open symbols) binding to G-quadruplex (black squares), G-quadruplex/i-motif complementary duplex (red circles) and i-motif DNA (green diamonds). Insert: UV melting profiles of G-quadruplex DNA (1 µM/strand) in the absence (blue) or presence of 1 µM P-enantiomer (cyan) or M-enantiomer (magenta) in 10 mM Tris buffer containing 100 mM NaCl, pH 7.2.
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Figure 2: Plot of DNA stabilization temperature versus the concentration of [Ni2L3]4+-P (filled symbols) or [Ni2L3]4+-M (open symbols) binding to G-quadruplex (black squares), G-quadruplex/i-motif complementary duplex (red circles) and i-motif DNA (green diamonds). Insert: UV melting profiles of G-quadruplex DNA (1 µM/strand) in the absence (blue) or presence of 1 µM P-enantiomer (cyan) or M-enantiomer (magenta) in 10 mM Tris buffer containing 100 mM NaCl, pH 7.2.

Mentions: The chiral selectivity on stabilization of human telomeric G-quadruplex DNA by [Ni2L3]4+-M and [Ni2L3]4+-P enantiomer is remarkable (Figure 2). Nonfluorescent-labeled DNA UV melting studies (7,8) directly demonstrate that P-enantiomer can increase G-quadruplex melting temperature (Tm) 10°C at 1:1 ratio of [complex]/[DNA], but M cannot increase Tm even at higher ratio (Figure 2). For i-motif DNA and G-quadruplex/i-motif complementary duplex DNA (4) (Figure 2), the two enantiomers do not show chiral selectivity. Both of them destabilize i-motif DNA and do not influence G-quadruplex/i-motif duplex DNA stability.Figure 2.


Chiral metallo-supramolecular complexes selectively recognize human telomeric G-quadruplex DNA.

Yu H, Wang X, Fu M, Ren J, Qu X - Nucleic Acids Res. (2008)

Plot of DNA stabilization temperature versus the concentration of [Ni2L3]4+-P (filled symbols) or [Ni2L3]4+-M (open symbols) binding to G-quadruplex (black squares), G-quadruplex/i-motif complementary duplex (red circles) and i-motif DNA (green diamonds). Insert: UV melting profiles of G-quadruplex DNA (1 µM/strand) in the absence (blue) or presence of 1 µM P-enantiomer (cyan) or M-enantiomer (magenta) in 10 mM Tris buffer containing 100 mM NaCl, pH 7.2.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 2: Plot of DNA stabilization temperature versus the concentration of [Ni2L3]4+-P (filled symbols) or [Ni2L3]4+-M (open symbols) binding to G-quadruplex (black squares), G-quadruplex/i-motif complementary duplex (red circles) and i-motif DNA (green diamonds). Insert: UV melting profiles of G-quadruplex DNA (1 µM/strand) in the absence (blue) or presence of 1 µM P-enantiomer (cyan) or M-enantiomer (magenta) in 10 mM Tris buffer containing 100 mM NaCl, pH 7.2.
Mentions: The chiral selectivity on stabilization of human telomeric G-quadruplex DNA by [Ni2L3]4+-M and [Ni2L3]4+-P enantiomer is remarkable (Figure 2). Nonfluorescent-labeled DNA UV melting studies (7,8) directly demonstrate that P-enantiomer can increase G-quadruplex melting temperature (Tm) 10°C at 1:1 ratio of [complex]/[DNA], but M cannot increase Tm even at higher ratio (Figure 2). For i-motif DNA and G-quadruplex/i-motif complementary duplex DNA (4) (Figure 2), the two enantiomers do not show chiral selectivity. Both of them destabilize i-motif DNA and do not influence G-quadruplex/i-motif duplex DNA stability.Figure 2.

Bottom Line: The chiral supramolecular complex has both small molecular chemical features and the large size of a zinc-finger-like DNA-binding motif.The complex is also convenient to synthesize and separate enantiomers.These results provide new insights into the development of chiral anticancer agents for targeting G-quadruplex DNA.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Inorganic Chemistry, Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

ABSTRACT
Here, we report the first example that one enantiomer of a supramolecular cylinder can selectively stabilize human telomeric G-quadruplex DNA. The P-enantiomer of this cylinder has a strong preference for G-quadruplex over duplex DNA and, in the presence of sodium, can convert G-quadruplexes from an antiparallel to a hybrid structure. The compound's chiral selectivity and its ability to discriminate quadruplex DNA have been studied by DNA melting, circular dichroism, gel electrophoresis, fluorescence spectroscopy and S1 nuclease cleavage. The chiral supramolecular complex has both small molecular chemical features and the large size of a zinc-finger-like DNA-binding motif. The complex is also convenient to synthesize and separate enantiomers. These results provide new insights into the development of chiral anticancer agents for targeting G-quadruplex DNA.

Show MeSH
Related in: MedlinePlus