Synthesis of 2′-hydrazine oligonucleotides and their efficient conjugation with aldehydes and 1,3-diketones

被引：8

作者：

Zatsepin, Timofei S.

Gait, Michael J.

Oretskaya, Tatiana S.

Stetsenko, Dmitry A. ^{[1
]}

机构：

[1] Univ Surrey, Sch Biomed & Mol Sci, Guildford GU2 7XH, Surrey, England

[2] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

[3] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia

来源：

TETRAHEDRON LETTERS | 2006年 / 47卷 / 31期

基金：

俄罗斯基础研究基金会; 英国惠康基金;

关键词：

modified oligonucleotides; conjugation; aldehyde; 1,3-diketone; hydrazone; pyrazole;

D O I：

10.1016/j.tetlet.2006.05.152

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Oligodeoxyribonucleotides that contain a novel nucleoside, 2'-O-(2-hydrazinoethyl)uridine were synthesised by NaBH3CN reduction of hydrazones formed from 2'-O-(2-oxoethyl)oligonucteotides with FmocNHNH(2), followed by concd aq NH3 deprotection. The T-hydrazine oligonucleotides obtained were then used to synthesise a number of conjugates with aldehydes via hydrazone formation and with 1,3-diketones via pyrazole formation. The method was shown to be applicable for the preparation of oligonucleotide-peptide conjugates. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5515 / 5518

页数：4

相关论文

共 19 条

[1] Peptide-mediated cellular delivery of antisense oligonucleotides and their analogues [J].

Gait, MJ .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2003, 60 (05) :844-853

[2] Nucleic acid duplexes incorporating a dissociable covalent base pair [J].

Gao, K ;

Orgel, LE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :14837-14842

[3] SYNTHESIS OF 5'-OLIGONUCLEOTIDE HYDRAZIDE DERIVATIVES AND THEIR USE IN PREPARATION OF ENZYME NUCLEIC-ACID HYBRIDIZATION PROBES [J].

GHOSH, SS ;

KAO, PM ;

KWOH, DY .

ANALYTICAL BIOCHEMISTRY, 1989, 178 (01) :43-51

[4]

Juliano RL, 2005, CURR OPIN MOL THER, V7, P132

[5] Synthesis of modified nucleotide building blocks containing electrophilic groups in the 2′-position [J].

Kachalova, AV ;

Zatsepin, TS ;

Romanova, EA ;

Stetsenko, DA ;

Gait, MJ ;

Oretskaya, TS .

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2000, 19 (10-12) :1693-1707

[6] NOVEL ADDUCTS FROM THE MODIFICATION OF NUCLEIC-ACID BASES BY MALONDIALDEHYDE [J].

NAIR, V ;

TURNER, GA ;

OFFERMAN, RJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1984, 106 (11) :3370-3371

[7] Reaction of malondialdehyde-DNA adducts with hydrazines-development of a facile assay for quantification of malondialdehyde equivalents in DNA [J].

Otteneder, M ;

Plastaras, JP ;

Marnett, LJ .

CHEMICAL RESEARCH IN TOXICOLOGY, 2002, 15 (03) :312-318

[8] Chemoselective ligation in glycochemistry [J].

Peri, F ;

Nicotra, F .

CHEMICAL COMMUNICATIONS, 2004, (06) :623-627

[9] Hydrazide oligonucleotides:: new chemical modification for chip array attachment and conjugation [J].

Raddatz, S ;

Mueller-Ibeler, J ;

Kluge, J ;

Wäss, L ;

Burdinski, G ;

Havens, JR ;

Onofrey, TJ ;

Wang, D ;

Schweitzer, M .

NUCLEIC ACIDS RESEARCH, 2002, 30 (21) :4793-4802

[10] Peptide conjugates of oligonucleotides as enhanced antisense agents [J].

Stetsenko, DA ;

Arzumanov, AA ;

Korshun, VA ;

Gait, MJ .

MOLECULAR BIOLOGY, 2000, 34 (06) :852-859