A bulge binding agent with novel wedge-shape topology for stimulation of DNA triplet repeat strand slippage synthesis

Liangliang Liu; Heyang Li; Long Yi; Xing Yang; Xin Wen; Zhen Xi

doi:10.1016/j.bmcl.2008.10.038

A bulge binding agent with novel wedge-shape topology for stimulation of DNA triplet repeat strand slippage synthesis

Liangliang Liu, Heyang Li, Long Yi, Xing Yang, Xin Wen, Zhen Xi

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Expansion of DNA repeat sequences is associated with many human genetic diseases. Bulged DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. Herein a bulge binding agent with novel wedge-shape topology of the aromatic moiety was designed and synthesized. The compound-bulge DNA interactions were characterized via UV melting experiments, circular dichroism and were quantitated by surface plasmon resonance with K_d of 41.5 μM. This compound showed remarkable stimulation for DNA triplet repeat strand slippage synthesis in vitro.

Original language	English (US)
Pages (from-to)	6184-6188
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2008.10.038
State	Published - Dec 1 2008
Externally published	Yes

Keywords

Bulge DNA
Phenothiazine
Slippage synthesis
Surface plasmon resonance
Wedge-shaped structure

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2008.10.038

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title = "A bulge binding agent with novel wedge-shape topology for stimulation of DNA triplet repeat strand slippage synthesis",

abstract = "Expansion of DNA repeat sequences is associated with many human genetic diseases. Bulged DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. Herein a bulge binding agent with novel wedge-shape topology of the aromatic moiety was designed and synthesized. The compound-bulge DNA interactions were characterized via UV melting experiments, circular dichroism and were quantitated by surface plasmon resonance with Kd of 41.5 μM. This compound showed remarkable stimulation for DNA triplet repeat strand slippage synthesis in vitro.",

keywords = "Bulge DNA, Phenothiazine, Slippage synthesis, Surface plasmon resonance, Wedge-shaped structure",

author = "Liangliang Liu and Heyang Li and Long Yi and Xing Yang and Xin Wen and Zhen Xi",

note = "Funding Information: This work was supported by the National Key Project for Basic Research of China (2003CB114403), National Natural Science Foundation of China (20272029, 20572053, 20421202, 20432010), Ministry of Education of China (104189), and Nankai University ISC. ",

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doi = "10.1016/j.bmcl.2008.10.038",

language = "English (US)",

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pages = "6184--6188",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

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T1 - A bulge binding agent with novel wedge-shape topology for stimulation of DNA triplet repeat strand slippage synthesis

AU - Liu, Liangliang

AU - Li, Heyang

AU - Yi, Long

AU - Yang, Xing

AU - Wen, Xin

AU - Xi, Zhen

N1 - Funding Information: This work was supported by the National Key Project for Basic Research of China (2003CB114403), National Natural Science Foundation of China (20272029, 20572053, 20421202, 20432010), Ministry of Education of China (104189), and Nankai University ISC.

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Expansion of DNA repeat sequences is associated with many human genetic diseases. Bulged DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. Herein a bulge binding agent with novel wedge-shape topology of the aromatic moiety was designed and synthesized. The compound-bulge DNA interactions were characterized via UV melting experiments, circular dichroism and were quantitated by surface plasmon resonance with Kd of 41.5 μM. This compound showed remarkable stimulation for DNA triplet repeat strand slippage synthesis in vitro.

AB - Expansion of DNA repeat sequences is associated with many human genetic diseases. Bulged DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. Herein a bulge binding agent with novel wedge-shape topology of the aromatic moiety was designed and synthesized. The compound-bulge DNA interactions were characterized via UV melting experiments, circular dichroism and were quantitated by surface plasmon resonance with Kd of 41.5 μM. This compound showed remarkable stimulation for DNA triplet repeat strand slippage synthesis in vitro.

KW - Bulge DNA

KW - Phenothiazine

KW - Slippage synthesis

KW - Surface plasmon resonance

KW - Wedge-shaped structure

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

A bulge binding agent with novel wedge-shape topology for stimulation of DNA triplet repeat strand slippage synthesis

Abstract

Keywords

ASJC Scopus subject areas

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