TY - JOUR
T1 - Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers
AU - Ries, Annika
AU - Kumar, Rajesh
AU - Lou, Chenguang
AU - Kosbar, Tamer
AU - Vengut-Climent, Empar
AU - Jørgensen, Per Trolle
AU - Morales, Juan C
AU - Wengel, Jesper
PY - 2016/10/13
Y1 - 2016/10/13
N2 - 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.
AB - 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.
KW - Biophysical Phenomena
KW - Carbon-13 Magnetic Resonance Spectroscopy
KW - DNA/chemistry
KW - Galactose/chemistry
KW - Models, Molecular
KW - Nucleic Acid Denaturation
KW - Oligonucleotides/chemistry
KW - Proton Magnetic Resonance Spectroscopy
KW - Spectrometry, Mass, Electrospray Ionization
KW - Temperature
U2 - 10.1021/acs.joc.6b01917
DO - 10.1021/acs.joc.6b01917
M3 - Journal article
C2 - 27736097
SN - 0022-3263
VL - 81
SP - 10845
EP - 10856
JO - The Journal of Organic Chemistry
JF - The Journal of Organic Chemistry
IS - 22
ER -