Effect of LNA- and OMeN-modified oligonucleotide probes on the stability and discrimination of mismatched base pairs of duplexes.

Journal of Biosciences
Ying YanYiFu Guan

Abstract

Locked nucleic acid (LNA) and 2'-O-methyl nucleotide (OMeN) are the most extensively studied nucleotide analogues. Although both LNA and OMeN are characterized by the C3'-endo sugar pucker conformation, which is dominant in A-form DNA and RNA nucleotides, they demonstrate different binding behaviours. Previous studies have focused attention on their properties of duplex stabilities, hybridization kinetics and resistance against nuclease digestion; however, their ability to discriminate mismatched hybridizations has been explored much less. In this study, LNA- and OMeN-modified oligonucleotide probes have been prepared and their effects on the DNA duplex stability have been examined: LNA modifications can enhance the duplex stability, whereas OMeN modifications reduce the duplex stability. Next, we studied how the LNA:DNA and OMeN:DNA mismatches reduced the duplex stability. Melting temperature measurement showed that different LNA:DNA or OMeN:DNA mismatches indeed influence the duplex stability differently. LNA purines can discriminate LNA:DNA mismatches more effectively than LNA pyrimidines as well as DNA nucleotides. Furthermore, we designed five LNA- and five OMeN-modified oligonucleotide probes to simulate realistic situati...Continue Reading

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Citations

Jul 16, 2014·Acta Biochimica Et Biophysica Sinica·Bin ZhaoYifu Guan
Mar 13, 2016·Applied Microbiology and Biotechnology·Sílvia FonteneteNuno Filipe Azevedo
Apr 5, 2015·Applied Microbiology and Biotechnology·Silvia FonteneteAzevedo Nuno Filipe
Feb 26, 2015·Neurodegenerative Disease Management·Lynn M Bekris, James B Leverenz
Apr 12, 2014·PLoS Computational Biology·Yunqiang BianWei Wang
May 18, 2016·Bioscience, Biotechnology, and Biochemistry·Yuuki MitsukawaJun Ogawa

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