A short, novel, and cheaper procedure for oligonucleotide synthesis using automated solid phase synthesizer

被引:24
作者
Song, QL [1 ]
Wang, ZW [1 ]
Sanghvi, YS [1 ]
机构
[1] ISIS Pharmaceut Inc, Carlsbad, CA 92008 USA
关键词
antisense; sulfur-transfer reagent; dimethylthiuram disulfide; oligonucleotide synthesis;
D O I
10.1081/NCN-120021968
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dimethylthiuram disulfide (DTD) has been developed as an efficient thiolation reagent during automated synthesis of oligonucleotides using phosphoramidite chemistry. Simultaneous thiolation and capping was accomplished by mixing DTD with capping solution B, which saved 20% of solvent consumption and compressed the four-step synthesis cycle to three. Large-scale (1 mmol) synthesis of phosphorothioate oligonucleotides has been demonstrated with excellent yield and purity.
引用
收藏
页码:629 / 633
页数:5
相关论文
共 14 条
[1]   Synthesis of antisense oligonucleotides: Replacement of 3H-1,2-benzodithiol-3-one 1,1-dioxide (Beaucage reagent) with phenylacetyl disulfide (PADS) as efficient sulfurization reagent: From bench to bulk manufacture of active pharmaceutical ingredient [J].
Cheruvallath, ZS ;
Carty, RL ;
Moore, MN ;
Capaldi, DC ;
Krotz, AH ;
Wheeler, PD ;
Turney, BJ ;
Craig, SR ;
Gaus, HJ ;
Scozzari, AN ;
Cole, DL ;
Ravikumar, VT .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2000, 4 (03) :199-204
[2]   NEW EFFICIENT SULFURIZING REAGENTS FOR THE PREPARATION OF OLIGODEOXYRIBONUCLEOTIDE PHOSPHOROTHIOATE ANALOGS [J].
EFIMOV, VA ;
KALINKINA, AL ;
CHAKHMAKHCHEVA, OG ;
HILL, TS ;
JAYARAMAN, K .
NUCLEIC ACIDS RESEARCH, 1995, 23 (20) :4029-4033
[3]   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
[4]   Synthesis of oligodeoxyribonucleoside phosphorothioates using Lawesson's reagent for the sulfur transfer step [J].
Ju, JY ;
McKenna, CE .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (12) :1643-1645
[5]   DIBENZOYL TETRASULFIDE - A RAPID SULFUR TRANSFER AGENT IN THE SYNTHESIS OF PHOSPHOROTHIOATE ANALOGS OF OLIGONUCLEOTIDES [J].
RAO, MV ;
REESE, CB ;
ZHAO, ZY .
TETRAHEDRON LETTERS, 1992, 33 (33) :4839-4842
[6]   SOLID-PHASE SYNTHESIS OF PHOSPHOROTHIOATE OLIGONUCLEOTIDES USING BENZYLTRIETHYLAMMONIUM TETRATHIOMOLYBDATE AS A RAPID SULFUR TRANSFER REAGENT [J].
RAO, MV ;
MACFARLANE, K .
TETRAHEDRON LETTERS, 1994, 35 (36) :6741-6744
[7]  
SANGHVI YS, 1999, MANUAL ANTISENSE MET, P3
[8]   BIS(O,O-DIISOPROPOXY PHOSPHINOTHIOYL) DISULFIDE - A HIGHLY EFFICIENT SULFURIZING REAGENT FOR COST-EFFECTIVE SYNTHESIS OF OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S [J].
STEC, WJ ;
UZNANSKI, B ;
WILK, A ;
HIRSCHBEIN, BL ;
FEARON, KL ;
BERGOT, BJ .
TETRAHEDRON LETTERS, 1993, 34 (33) :5317-5320
[9]   Large-scale synthesis of oligonucleotide phosphorothioates using 3-amino-1,2,4-dithiazole-5-thione as an efficient sulfur-transfer reagent [J].
Tang, JY ;
Han, YX ;
Tang, JX ;
Zhang, ZD .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2000, 4 (03) :194-198
[10]   On inventing reactions for atom economy [J].
Trost, BM .
ACCOUNTS OF CHEMICAL RESEARCH, 2002, 35 (09) :695-705