Synthesis and Biophysical Studies of N2′-Functionalized 2′-Amino-α-L-LNA

Abstract

A synthetic route towards a selected set of N-acylated and N-alkylated derivatives of 2 ′-amino-α-L-LNA phosphoramidite building blocks has been developed. Biophysical studies suggest that the 2-oxo-5-azabicyclo[2.2.1]heptane skeleton of 2 ′-amino-α-L-LNA allows precise positioning of intercalators in the core of nucleic acid duplexes.

Keywords:

• 2′-Amino-α-L-LNA
• pyrene
• oligonucleotides
• intercalation

We greatly appreciate funding from The Danish National Research Foundation.

Notes

^a T _m values of unmodified duplex (where B = T) toward its complementary DNA and RNA are 28.5°C and 24.5°C, respectively.

^b Thermal denaturation temperatures recorded in medium salt buffer ([Na⁺] = 110 mM, [Cl⁻] = 100 mM, pH 7.0 (adjusted with 10 mM NaH₂PO₄/5 mM Na₂HPO₄)), using 1.0 μM concentrations of the two complementary strands. See synthetic scheme for structure of monomers.