Title

PHENANTHROLINE BASED METAL COMPLEXES AS G-QUADRUPLEX BINDING LIGANDS

Lead Author Affiliation

Chemistry

Second Author Affiliation

Chemistry

Third Author Affiliation

Chemistry

Fourth Author Affiliation

Chemistry

Fifth Author Affiliation

Chemistry

Sixth Author Affiliation

Chemistry

Introduction

Telomeric DNA present at the ends of chromosomes in normal somatic cells is progressively shortened after each cell replication, which eventually triggers cell death. In contrast, the length of telomeric DNA in cancer cells is maintained by over-expressed telomerase, a reverse transcriptase, making cancer cells immortal. Due to this apparent difference, telomerase has recently emerged as an attractive target for cancer intervention. One of the efficient approaches to inhibit the telomerase activity is to induce G-quadruplex formation in the telomeric DNA regions by small molecules to block the binding of telomerase. Such small molecules, known as G-quadruplex binding ligands, are being developed as potential anti-cancer drugs.

Purpose

In this present work, we investigate the binding of newly developed phenanthroline metal complexes with G-quadruplex DNA and their cytotoxicity towards three cancer cell lines.

Method

Several biophysical techniques including thermal denaturation, fluorescence titration, UV absorbance, and circular dichroism were used to obtain the binding affinity and specificity. The MTS cell viability assay was used for studying cytotoxicity.

Results

Our results demonstrated that phenanthroline-metal complexes can selectively bind to G-quadruplex over duplex with high affinities partly due to the enhanced planar complex aromatic surface. In addition, properly designed side chains can further improve the stabilization effect.

Significance

This is the first report showing that the 5-substituted phenanthroline derivatives in the presence of divalent metal ions can efficiently stabilize G-quadruplex DNA. The metal ion mediated G4 stabilization suggests a promising strategy to achieve new chemical entities for drug design and development.

Location

DeRosa University Center, Stockton campus, University of the Pacific

Format

Poster Presentation

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Mar 25th, 10:00 AM Mar 25th, 3:00 PM

PHENANTHROLINE BASED METAL COMPLEXES AS G-QUADRUPLEX BINDING LIGANDS

DeRosa University Center, Stockton campus, University of the Pacific

Telomeric DNA present at the ends of chromosomes in normal somatic cells is progressively shortened after each cell replication, which eventually triggers cell death. In contrast, the length of telomeric DNA in cancer cells is maintained by over-expressed telomerase, a reverse transcriptase, making cancer cells immortal. Due to this apparent difference, telomerase has recently emerged as an attractive target for cancer intervention. One of the efficient approaches to inhibit the telomerase activity is to induce G-quadruplex formation in the telomeric DNA regions by small molecules to block the binding of telomerase. Such small molecules, known as G-quadruplex binding ligands, are being developed as potential anti-cancer drugs.