G-quadruplex structure of an anti-proliferative DNA sequence

• Main Authors: Do, Ngoc Quang, Chung, Wan Jun, Truong, Thi Hong Anh, Heddi, Brahim, Phan, Anh Tuân
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2017
• Subjects: Cancer; DNA
• Online Access: https://hdl.handle.net/10356/84060; http://hdl.handle.net/10220/42925
• Institution: Nanyang Technological University

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 co-existence 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.