A two-step sulfurization for efficient solution-phase synthesis of phosphorothioate oligonucleotides

被引：6

作者：

Ghisaidoobe, Amar B. T. ^{[1
]}

de Koning, Martijn C. ^{[1
]}

Duynstee, Howard I. ^{[2
]}

Ten Kortenaar, Paul B. W. ^{[2
]}

Overkleeft, Herman S. ^{[1
]}

Filippov, Dmitri V. ^{[1
]}

van der Marel, Gijs A. ^{[1
]}

机构：

[1] Gorlaeus Labs, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands

[2] Diosynth Int BV, NL-5340 BH Oss, Netherlands

来源：

TETRAHEDRON LETTERS | 2008年 / 49卷 / 19期

关键词：

D O I：

10.1016/j.tetlet.2008.03.025

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A solution-phase approach for the synthesis of phosphorothioate oligonucleotides that circumvents the use of chromatographic purifications of protected phosphorothioate intermediates was developed. Implementation of a two-step sulfurization protocol in the phosphoramidite method allows efficient isolation of the intermediate phosphorothioates by extractions. The viability of this approach is demonstrated by the synthesis of a hexameric phosphorothioate oligonucleotide fragment. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3129 / 3132

页数：4

共 26 条

[1] Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition [J].

Bauer, S ;

Kirschning, CJ ;

Häcker, H ;

Redecke, V ;

Hausmann, S ;

Akira, S ;

Wagner, H ;

Lipford, GB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :9237-9242

[2]

CROOK ST, 2001, ANTISENSE DRUG TECHN

[3] Progress in antisense technology [J].

Crooke, ST .

ANNUAL REVIEW OF MEDICINE, 2004, 55 :61-95

[4] Simple and efficient solution-phase synthesis of oligonucleotides using extractive work-up [J].

de Koning, Martijn C. ;

Ghisaidoobe, Amar B. T. ;

Duynstee, Howard I. ;

Ten Kortenaar, Paul B. W. ;

Filippov, Dmitri V. ;

van der Marel, Gijs A. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2006, 10 (06) :1238-1245

[5] Antisense oligonucleotide-based therapeutics for cancer [J].

Dean, NM ;

Bennett, CF .

ONCOGENE, 2003, 22 (56) :9087-9096

[6] siRNAs: Applications in functional genomics and potential as therapeutics [J].

Dorsett, Y ;

Tuschl, T .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) :318-329

[7] Phosphorothioate oligodeoxynucleotides: What is their origin and what is unique about them? [J].

Eckstein, F .

ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 2000, 10 (02) :117-121

[8] Innate immune recognition of, and regulation by, DNA [J].

Ishii, Ken J. ;

Akira, Shizuo .

TRENDS IN IMMUNOLOGY, 2006, 27 (11) :525-532

[9] THE AUTOMATED SYNTHESIS OF SULFUR-CONTAINING OLIGODEOXYRIBONUCLEOTIDES USING 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE AS A SULFUR-TRANSFER REAGENT [J].

IYER, RP ;

PHILLIPS, LR ;

EGAN, W ;

REGAN, JB ;

BEAUCAGE, SL .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (15) :4693-4699

[10] AN EFFICIENT APPROACH TOWARD THE SYNTHESIS OF PHOSPHOROTHIOATE DIESTERS VIA THE SCHONBERG REACTION [J].

KAMER, PCJ ;

ROELEN, HCPF ;

VANDENELST, H ;

VANDERMAREL, GA ;

VANBOOM, JH .

TETRAHEDRON LETTERS, 1989, 30 (48) :6757-6760

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