Trityl tags for encoding in combinatorial synthesis

被引:39
作者
Shchepinov, MS [1 ]
Chalk, R [1 ]
Southern, EM [1 ]
机构
[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
关键词
combinatorial chemistry; mass spectrometry; nucleic acids; phosphoramidites;
D O I
10.1016/S0040-4020(00)00223-4
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
New tags and an encoding strategy for combinatorial synthesis are described. Combinatorial libraries of short oligonucleotides attached to TentaGel beads were synthesised by a split-and-mix strategy using 5'-DMTr or 5' Fmoc-protected nucleoside phosphoramidites. Trityl moieties with different masses were used to tag the nature and position of monomer units (bases) coupled at each step in the synthesis. Beads with a specific oligonucleotide were selected by hybridisation from combinatorial libraries. Tags orthogonal to the added nucleotides were produced by coupling amines of different molecular masses to an activated carboxyl group(s) on the trityl moiety. The tags may be released from the support by an acidic treatment or laser irradiation and then analysed by (MA)LDI-TOF. These properties make trityl-based tags promising for encoding in strategies not involving strong acids, such as oligonucleotide and peptide synthesis and small molecule combinatorial libraries. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:2713 / 2724
页数:12
相关论文
共 60 条
[1]   ENCODED COMBINATORIAL CHEMISTRY [J].
BRENNER, S ;
LERNER, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5381-5383
[2]   Split-split. A multiple synthesiser approach to efficient automated parallel synthesis [J].
Brooking, P ;
Doran, A ;
Grimsey, P ;
Hird, NW ;
MacLachlan, WS ;
Vimal, M .
TETRAHEDRON LETTERS, 1999, 40 (07) :1405-1408
[3]   A MASS-SPECTROMETRIC SOLUTION TO THE ADDRESS PROBLEM OF COMBINATORIAL LIBRARIES [J].
BRUMMEL, CL ;
LEE, INW ;
ZHOU, Y ;
BENKOVIC, SJ ;
WINOGRAD, N .
SCIENCE, 1994, 264 (5157) :399-402
[4]   Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide bead-bound combinatorial libraries [J].
Brummel, CL ;
Vickerman, JC ;
Carr, SA ;
Hemling, ME ;
Roberts, GD ;
Johnson, W ;
Weinstock, J ;
Gaitanopoulos, D ;
Benkovic, SJ ;
Winograd, N .
ANALYTICAL CHEMISTRY, 1996, 68 (02) :237-242
[5]   CHEMICAL SYNTHESIS OF DNA AND DNA ANALOGS [J].
CARUTHERS, MH .
ACCOUNTS OF CHEMICAL RESEARCH, 1991, 24 (09) :278-284
[6]   Synthesis and screening of linear and cyclic oligocarbamate libraries. Discovery of high affinity ligands for GPIIb/IIIa [J].
Cho, CY ;
Youngquist, RS ;
Paikoff, SJ ;
Beresini, MH ;
Hebert, AR ;
Berleau, LT ;
Liu, CW ;
Wemmer, DE ;
Keough, T ;
Schultz, PG .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (31) :7706-7718
[7]   NPIT - A NEW REAGENT FOR QUANTITATIVELY MONITORING REACTIONS OF AMINES IN COMBINATORIAL SYNTHESIS [J].
CHU, SS ;
REICH, SH .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (10) :1053-1058
[8]  
Coull JM, 1995, Patent USA, Patent No. [5410068, 5,410,068]
[9]   Encoding methods for combinatorial chemistry [J].
Czarnik, AW .
CURRENT OPINION IN CHEMICAL BIOLOGY, 1997, 1 (01) :60-66
[10]   LINKERS FOR COMBINATORIAL CHEMISTRY AND REACTION ANALYSIS USING SOLID-PHASE IN-SITU MASS-SPECTROMETRY [J].
EGNER, BJ ;
CARDNO, M ;
BRADLEY, M .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1995, (21) :2163-2164