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G-quadruplex structure of an anti-proliferative DNA sequence.

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 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.

SUBMITTER: Do NQ

PROVIDER: S-EPMC5499593 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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G-quadruplex structure of an anti-proliferative DNA sequence.

Do Ngoc Quang NQ Chung Wan Jun WJ Truong Thi Hong Anh THA Heddi Brahim B Phan Anh Tuân AT

Nucleic acids research 20170701 12

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 c ...[more]

PMID: 28549181

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