Combining a Ru(II) “Building Block” and Rapid Screening Approach to Identify DNA Structure-Selective “Light Switch” Compounds

Erin Wachter; Diego Moyá; Edith C. Glazer

doi:10.1021/acscombsci.6b00119

Combining a Ru(II) “Building Block” and Rapid Screening Approach to Identify DNA Structure-Selective “Light Switch” Compounds

Erin Wachter, Diego Moyá, Edith C. Glazer

Chemistry

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

9 Scopus citations

Abstract

A chemically reactive Ru(II) “building block”, able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent “light switch” dipyrido-[3,2-a:2′,3′-c] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA. Combining these two approaches allowed for the identification of hit molecules that showed different selectivities for biologically relevant DNA structures, particularly triplex and quadruplex DNA.

Original language	English
Pages (from-to)	85-95
Number of pages	11
Journal	ACS Combinatorial Science
Volume	19
Issue number	2
DOIs	https://doi.org/10.1021/acscombsci.6b00119
State	Published - Feb 13 2017

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

Funding

This work was supported by the National Institutes of Health (1R01GM107586). E.W. acknowledges the University of Kentucky Research Challenge Trust Fund for providing fellowship support. Some chemical analysis was performed at the University of Kentucky Environmental Research Training Laboratory (ERTL). The luminescent experiments were performed using a plate reader in the Center for Molecular Medicine Protein Core, which is funded through NIH/NIGMS COBRE grant P30GM110787.

Funders	Funder number
Environmental Research and Training Laboratory (ERTL)
NIH/NIGMS	P30GM110787
University of Kentucky Environmental Research Training Laboratory
University of Kentucky Research Challenge Trust Fund
National Institutes of Health (NIH)
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	R01GM107586
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences

Keywords

DNA structure-selective
Ru(II)
biologically relevant
library
parallel screening
“light switch” compounds

ASJC Scopus subject areas

General Chemistry

Access to Document

10.1021/acscombsci.6b00119

Cite this

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abstract = "A chemically reactive Ru(II) “building block”, able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent “light switch” dipyrido-[3,2-a:2′,3′-c] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA. Combining these two approaches allowed for the identification of hit molecules that showed different selectivities for biologically relevant DNA structures, particularly triplex and quadruplex DNA.",

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AB - A chemically reactive Ru(II) “building block”, able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent “light switch” dipyrido-[3,2-a:2′,3′-c] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA. Combining these two approaches allowed for the identification of hit molecules that showed different selectivities for biologically relevant DNA structures, particularly triplex and quadruplex DNA.

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Combining a Ru(II) “Building Block” and Rapid Screening Approach to Identify DNA Structure-Selective “Light Switch” Compounds

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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