2′-N-Alkylaminocarbonyl-2′-amino-LNA: Synthesis, duplex stability, nuclease resistance, and in vitro anti-microRNA activity

[Display omitted] 2′-Amino-LNA has the potential to acquire various functions through chemical modification at the 2′-nitrogen atom. This study focused on 2′-N-alkylaminocarbonyl 2′-amino-LNA, which is a derivative of 2′-amino-LNA. We evaluated its practical usefulness as a chemical modification of anti-miRNA oligonucleotide. The synthesis of phosphoramidites of 2′-N-alkylaminocarbonyl substituted 2′-amino-LNA bearing thymine and 5-methylcytosine proceeded in good yields. Incorporating the 2′-N-alkylaminocarbonyl-2′-amino-LNA monomers into oligonucleotides improved the duplex stability for complementary RNA strands and robust nuclease resistance. Moreover, 2′-N-alkylaminocarbonyl-2′-amino-LNA is a promising scaffold that significantly increases the potency of anti-miRNA oligonucleotides.