Work

Trisubstituted Isoalloxazines as a New Class of G-Quadruplex Binding Ligands: Small Molecule Regulation of c-kit Oncogene Expression

Year: 2007

Type: article

Abstract: Herein, we report the design, synthesis, biophysical evaluation with primary biological data of 3,8,10-trisubstituted isoalloxazines as a new class of G-quadruplex binding ligands. We have developed a short and robust synthesis for trisubstituted isoalloxazines in good yields. The G-quadruplex binding and stabilization potential of isoalloxazines was assessed by surface plasmon resonance and fluorescence resonance energy transfer assay. The data revealed that these isoalloxazines bind and stabilize G-quadruplex DNA, but not duplex DNA, and exhibit potential for discriminating between DNA quadruplexes. Cell-based experiments using cell lines that express the proto-oncogene c-kit (MCF-7 and HGC-27) showed that such isoalloxazines can inhibit the expression of c-kit.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja075881p

Authors: Mallesham Bejugam, Sven Sewitz, Pravin S. Shirude, Raphaël Rodriguez, Ramla Shahid, Shankar Balasubramanian

Institution: University of Cambridge

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: Cancer Research UK

Award: G4470602312