Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA, and 2'-Amino-LNA Monomers

J Org Chem. 2016 Nov 18;81(22):10845-10856. doi: 10.1021/acs.joc.6b01917. Epub 2016 Oct 25.

Abstract

Galactose-modified thymidine, LNA-T, and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, the 2'-amino-LNA-T derivatives induced remarkable 3'-exonuclease resistance. These results were further investigated using molecular modeling studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysical Phenomena
  • Carbon-13 Magnetic Resonance Spectroscopy
  • DNA / chemistry*
  • Galactose / chemistry*
  • Models, Molecular
  • Nucleic Acid Denaturation
  • Oligonucleotides / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Spectrometry, Mass, Electrospray Ionization
  • Temperature

Substances

  • Oligonucleotides
  • amino-LNA
  • locked nucleic acid
  • DNA
  • Galactose