Methylphosphonate LNA: A locked nucleic acid with a methylphosphonate linkage

被引:8
作者
Lauritsen, A
Dahl, BM
Dahl, O
Vester, B
Wengel, J
机构
[1] Univ So Denmark, Nucle Acid Ctr, Dept Chem, DK-5230 Odense M, Denmark
[2] Univ Copenhagen, Dept Chem, DK-2100 Copenhagen, Denmark
[3] Univ So Denmark, Nucle Acid Ctr, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark
关键词
D O I
10.1016/S0960-894X(02)00882-X
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Synthesis of an oligonucleotide containing one methylphosphonate locked nucleic acid (LNA) thymine monomer using the phosphoramidite approach is described. The binding affinity of this 9-mer methylphosphonate LNA towards complementary DNA and RNA oligonucleotides was increased compared to the reference DNA, but decreased compared to the reference LNA. In the 9-mer sequence context studied, introduction of a single methylphosphonate LNA monomer, contrary to a single LNA monomer, efficiently inhibits 3-exonucleolytic degradation. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:253 / 256
页数:4
相关论文
共 26 条
[1]   OLIGODEOXYNUCLEOSIDE METHYLPHOSPHONATES - SYNTHESIS AND ENZYMATIC DEGRADATION [J].
AGRAWAL, S ;
GOODCHILD, J .
TETRAHEDRON LETTERS, 1987, 28 (31) :3539-3542
[2]   Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA [J].
Braasch, DA ;
Corey, DR .
CHEMISTRY & BIOLOGY, 2001, 8 (01) :1-7
[3]   ANTISENSE OLIGONUCLEOTIDES [J].
DEMESMAEKER, A ;
HANER, R ;
MARTIN, P ;
MOSER, HE .
ACCOUNTS OF CHEMICAL RESEARCH, 1995, 28 (09) :366-374
[4]   The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes [J].
Freier, SM ;
Altmann, KH .
NUCLEIC ACIDS RESEARCH, 1997, 25 (22) :4429-4443
[5]   LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition [J].
Koshkin, AA ;
Singh, SK ;
Nielsen, P ;
Rajwanshi, VK ;
Kumar, R ;
Meldgaard, M ;
Olsen, CE ;
Wengel, J .
TETRAHEDRON, 1998, 54 (14) :3607-3630
[6]   A simplified and efficient route to 2′-O, 4′-C-methylene-linked bicyclic ribonucleosides (locked nucleic acid) [J].
Koshkin, AA ;
Fensholdt, J ;
Pfundheller, HM ;
Lomholt, C .
JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (25) :8504-8512
[7]   Design of antisense oligonucleotides stabilized by locked nucleic acids [J].
Kurreck, J ;
Wyszko, E ;
Gillen, C ;
Erdmann, VA .
NUCLEIC ACIDS RESEARCH, 2002, 30 (09) :1911-1918
[8]   Antisense molecules and furanose conformations -: is it really that simple? [J].
Kværno, L ;
Wengel, J .
CHEMICAL COMMUNICATIONS, 2001, (16) :1419-1424
[9]  
Kværno L, 2000, J ORG CHEM, V65, P5167
[10]   Oligodeoxynucleotides containing amide-linked LNA-type dinucleotides: synthesis and high-affinity nucleic acid hybridization [J].
Lauritsen, A ;
Wengel, J .
CHEMICAL COMMUNICATIONS, 2002, (05) :530-531