G-quadruplex structure of an anti-proliferative DNA sequence

July 28, 2017

Title

G-quadruplex structure of an anti-proliferative DNA sequence

Author

Ngoc Quang Do, Wan Jun Chung, Thi Hong Anh Truong, Brahim Heddi, Anh Tuan Phan

Year

2017

Journal

Nucleic Acids Research

Abstract

AGRO100 (also known as AS1411) is a G-rich oligonucleotide that has long been established as a potent anti-cancer aptamer. However, the structure of AGRO100 remained unresolved, due to the coexistence of multiple different G-quadruplex conformations. We identified a DNA sequence named AT11, derived from AGRO100, which formed a single major G-quadruplex conformation and exhibited a similar anti-proliferative activity as AGRO100. The solution structure of AT11 revealed a four-layer G-quadruplex comprising of two propeller-type parallel-stranded subunits connected through a central linker. The stacking between the two subunits occurs at the 3 - end of the first block and the 5 -end of the second block. The structure of the anti-proliferative DNA sequence AT11 will allow greater understanding on the G-quadruplex folding principles and aid in structural optimization of anti-proliferative oligonucleotides.

Instrument

J-815

Keywords

Circular dichroism, DNA structure, Biochemistry