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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
2'-N-Alkylaminocarbonyl-2'-amino-LNA: Synthesis, duplex stability, nuclease resistance, and in vitro anti-microRNA
Tomo Takegawa-Araki1, Kai Yasukawa1, Norihiko Iwazaki1
1Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Shonan Health Innovation Park, 2-26-1, Muraoka-Higashi, Fujisawa, Kanagawa 251-8555, Japan.
Abstract:
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.
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