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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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Native gel electrophoretic analysis (20% PAGE) of human telomeric d[AG3(T2AG3)3] in the presence of various concentration of [Ni2L3]4+ (A and C) and [Fe2L3]4+ (B and D). The gels were run in TB buffer with 10 mM NaCl (A and B) or 10 mM KCl (C and D). Lane 1 was the DNA alone. Samples of lanes 2–4 were prepared as DNA with P-enantiomer at the ratios of 2:1, 1:1 and 2:3. Samples of lanes 5–7 were prepared as DNA with M-enantiomer at the ratios of 2:1, 1:1 and 2:3.
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Figure 3: Native gel electrophoretic analysis (20% PAGE) of human telomeric d[AG3(T2AG3)3] in the presence of various concentration of [Ni2L3]4+ (A and C) and [Fe2L3]4+ (B and D). The gels were run in TB buffer with 10 mM NaCl (A and B) or 10 mM KCl (C and D). Lane 1 was the DNA alone. Samples of lanes 2–4 were prepared as DNA with P-enantiomer at the ratios of 2:1, 1:1 and 2:3. Samples of lanes 5–7 were prepared as DNA with M-enantiomer at the ratios of 2:1, 1:1 and 2:3.

Mentions: The chiral selectivity of the two enantiomers binding to human telomeric G-quadruplex is further studied by gel electrophoresis (Figure 3). In the presence of P-enantiomer, a new band with mobility slower than that of G-quadruplex DNA alone was observed. The retarded migration is due to the molecular weight/charge contribution of supramolecule to supramolecule–quadruplex complex (25). While in the presence of M-enantiomer, no delayed band was observed (Figure 3). These results are in accordance with DNA melting data (Figure 2).Figure 3.


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)

Native gel electrophoretic analysis (20% PAGE) of human telomeric d[AG3(T2AG3)3] in the presence of various concentration of [Ni2L3]4+ (A and C) and [Fe2L3]4+ (B and D). The gels were run in TB buffer with 10 mM NaCl (A and B) or 10 mM KCl (C and D). Lane 1 was the DNA alone. Samples of lanes 2–4 were prepared as DNA with P-enantiomer at the ratios of 2:1, 1:1 and 2:3. Samples of lanes 5–7 were prepared as DNA with M-enantiomer at the ratios of 2:1, 1:1 and 2:3.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 3: Native gel electrophoretic analysis (20% PAGE) of human telomeric d[AG3(T2AG3)3] in the presence of various concentration of [Ni2L3]4+ (A and C) and [Fe2L3]4+ (B and D). The gels were run in TB buffer with 10 mM NaCl (A and B) or 10 mM KCl (C and D). Lane 1 was the DNA alone. Samples of lanes 2–4 were prepared as DNA with P-enantiomer at the ratios of 2:1, 1:1 and 2:3. Samples of lanes 5–7 were prepared as DNA with M-enantiomer at the ratios of 2:1, 1:1 and 2:3.
Mentions: The chiral selectivity of the two enantiomers binding to human telomeric G-quadruplex is further studied by gel electrophoresis (Figure 3). In the presence of P-enantiomer, a new band with mobility slower than that of G-quadruplex DNA alone was observed. The retarded migration is due to the molecular weight/charge contribution of supramolecule to supramolecule–quadruplex complex (25). While in the presence of M-enantiomer, no delayed band was observed (Figure 3). These results are in accordance with DNA melting data (Figure 2).Figure 3.

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