Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker

Yongjun Chu; Vincent Lynch; Brent L. Iverson

doi:10.1016/j.tet.2006.03.038

Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker

Yongjun Chu, Vincent Lynch, Brent L. Iverson

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

20 Scopus citations

Abstract

Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.

Original language	English (US)
Pages (from-to)	5536-5548
Number of pages	13
Journal	Tetrahedron
Volume	62
Issue number	23
DOIs	https://doi.org/10.1016/j.tet.2006.03.038
State	Published - Jun 5 2006

Keywords

Bis-intercalator
Dissociation kinetics
Polyintercalation
Rigid
Spiro-cyclic linker

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2006.03.038

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title = "Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker",

abstract = "Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.",

keywords = "Bis-intercalator, Dissociation kinetics, Polyintercalation, Rigid, Spiro-cyclic linker",

author = "Yongjun Chu and Vincent Lynch and Iverson, {Brent L.}",

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T1 - Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker

AU - Chu, Yongjun

AU - Lynch, Vincent

AU - Iverson, Brent L.

N1 - Funding Information: This work was supported by the National Institutes of Health (GM-069647).

PY - 2006/6/5

Y1 - 2006/6/5

N2 - Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.

AB - Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.

KW - Bis-intercalator

KW - Dissociation kinetics

KW - Polyintercalation

KW - Rigid

KW - Spiro-cyclic linker

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DO - 10.1016/j.tet.2006.03.038

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JO - Tetrahedron

JF - Tetrahedron

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Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker

Abstract

Keywords

ASJC Scopus subject areas

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