Design and Synthesis of New Acid Cleavable Linkers for DNA Sequencing by Synthesis

Min Jiang; Daonian Tang; Xiaodong Zhao; Qing Li; Yuan Zhuang; Xiaofei Wei; Xiaowei Li; Yazhi Liu; Xin Yan Wu; Zhifeng Shao; Bing Gong; Yu Mei Shen

doi:10.1080/15257770.2014.945647

Design and Synthesis of New Acid Cleavable Linkers for DNA Sequencing by Synthesis

Min Jiang
, Daonian Tang
, Xiaodong Zhao
, Qing Li
, Yuan Zhuang
, Xiaofei Wei
, Xiaowei Li
, Yazhi Liu
, Xin Yan Wu
, Zhifeng Shao
, Bing Gong
, Yu Mei Shen

Chemistry

Shanghai Jiao Tong University
East China University of Science and Technology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2′-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by ¹H-NMR, ³¹P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.

Original language	English
Pages (from-to)	774-785
Number of pages	12
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	33
Issue number	12
DOIs	https://doi.org/10.1080/15257770.2014.945647
State	Published - Dec 2 2014

Keywords

fluorescent base analogues
syntheticmethodology
Triphosphate analogues

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10.1080/15257770.2014.945647

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title = "Design and Synthesis of New Acid Cleavable Linkers for DNA Sequencing by Synthesis",

abstract = "A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2′-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H-NMR, 31P-NMR, and HRMS with purity of up to 99\%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.",

keywords = "fluorescent base analogues, syntheticmethodology, Triphosphate analogues",

author = "Min Jiang and Daonian Tang and Xiaodong Zhao and Qing Li and Yuan Zhuang and Xiaofei Wei and Xiaowei Li and Yazhi Liu and Wu, \{Xin Yan\} and Zhifeng Shao and Bing Gong and Shen, \{Yu Mei\}",

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year = "2014",

month = dec,

day = "2",

doi = "10.1080/15257770.2014.945647",

language = "English",

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TY - JOUR

T1 - Design and Synthesis of New Acid Cleavable Linkers for DNA Sequencing by Synthesis

AU - Jiang, Min

AU - Tang, Daonian

AU - Zhao, Xiaodong

AU - Li, Qing

AU - Zhuang, Yuan

AU - Wei, Xiaofei

AU - Li, Xiaowei

AU - Liu, Yazhi

AU - Wu, Xin Yan

AU - Shao, Zhifeng

AU - Gong, Bing

AU - Shen, Yu Mei

PY - 2014/12/2

Y1 - 2014/12/2

N2 - A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2′-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H-NMR, 31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.

AB - A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2′-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H-NMR, 31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.

KW - fluorescent base analogues

KW - syntheticmethodology

KW - Triphosphate analogues

UR - https://www.scopus.com/pages/publications/84910110393

U2 - 10.1080/15257770.2014.945647

DO - 10.1080/15257770.2014.945647

M3 - Article

C2 - 25372993

AN - SCOPUS:84910110393

SN - 1525-7770

VL - 33

SP - 774

EP - 785

JO - Nucleosides, Nucleotides and Nucleic Acids

JF - Nucleosides, Nucleotides and Nucleic Acids

IS - 12

ER -

Design and Synthesis of New Acid Cleavable Linkers for DNA Sequencing by Synthesis

Abstract

Keywords

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