Locked nucleic acids

SSCP, single-strand conformation polymorphism PNA-LNA, peptide nucleic acid-locked nucleic acid MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ARMS, amplified refractory mutation system dHPLC, denaturing high performance liquid chromatography. 

Synthesis of 3 -C- and 4 -C-branched oligodeoxynucleotides and the development of locked nucleic acids (LNA) 99ACR301. 

Locked nucleic acid (LNA) Peptide nucleic acid (PNA) Morpholine phosphoroamidate (MF)... 

Wahlestedt C, Salmi P, Good L, Kela J, Johnsson T, Hokfelt T, Broberger C, Porreca F, Lai J, Ren K, Ossipov M, Koshkin A, Jakobsen N, Skouv J, Oerum H, Jacobsen MH, Wengel J (2000) Potent and nontoxic antisense oligonucleotides containing locked nucleic acids, Proc Natl Acad Sd USA 97 5633-5638... 

Rill, RL Ramey, BA Van Winkle, DH Locke, BR, Capillary Gel Electrophoresis of Nucleic Acids in Pluronic F127 Copolymer Liquid Crystals, Chromatographia Supplement I, Vol 49, S65, 1999. 

Veedu RN, Wengel J (2009) Locked nucleic acid as a novel class of therapeutic agents. RNA Biol 6 321-323... 

Grunweller A, Wyszko E, Bieber B et al (2003) Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2 -O-methyl RNA, phosphorothioates and small interfering RNA. Nucleic Acids Res 31 3185-3193... 

Key words MicroRNA, Locked nucleic acid, In situ hybridization, Immunohistochemistry,... 

Fig. 7.16 LAN (Locked nucleic acid) nucleosides as conformationally constrained nucleoside-derived A3 AR antagonists...

Kurreck, J., E. Wyszko, C. Gillen and V. A. Erdmann (2002). Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Res 30(9) 1911-8. 

Other backbone replacements displayed pairing strengths comparable with that seen in RNA but did not cross-bind with natural RNA and DNA. The exceptional cases are the locked nucleic acids of Wengel et al.11 and the threose nucleic acid analogues of Krishnamurthy and Eschenmoser.12... 

Fig. 1 Modified nucleic acids with enhanced nuclease stability, a DNA, b phosphorothioate, c Z -OjT-C-methylene-bridged (locked) nucleic acid (LNA), d 2f-0,A -C-ethylene-bridged nucleic acid (ENA), e Z -O-methyl nucleic acid, f methylphosphonate-linked nucleic acid, g morpholino-linked nucleic acid, h peptide nucleic acid (PNA)...

These applications require the use of FON probes resistant to nucleases. ONs with modified backbones such as oligo-2 -0-methyl-2 -deoxyribonucleotides (19), oligo-a-deoxy ribonucleotides (29), peptide nucleic acids (33) and locked nucleic acids (LNA) (50) (Fig. 4) are often used because of the commercially available building blocks. They form, with the RNA targets, hybrids that are not RNAse H substrates unless they can stimulate degradation of the targets rather than report on their presence. 

Locked Nucleic Acid (LNA) was presented in 1998. LNA represents a true member of the third generation of antisense drugs. When LNA nucleotides were incorporated into oligonucleotides, they induced the highest binding affinity for both complementary RNA and DNA reported in the field (2). This opened completely new perspectives for the development of antisense drugs. The remaining part of this article will focus on LNA and its therapeutic aspects. 

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