Issue 1, 2011

Amino acids attached to 2′-amino-LNA: synthesis and excellent duplex stability

Abstract

The synthesis of 2′-amino-LNA (the 2′-amino derivative of locked nucleic acid) has opened up a number of exciting possibilities with respect to modified nucleic acids. While maintaining the excellent duplex stability inferred by LNA-type oligonucleotides, the nitrogen in the 2′-position of 2′-amino-LNA monomers provides an excellent handle for functionalisation. Herein, the synthesis of amino acid functionalised 2′-amino-LNA derivatives is described. Following ON synthesis, a glycyl unit attached to the N2′-position of 2′-amino-LNA monomers was further acylated with a variety of amino acids. On binding to DNA/RNA complements, the modified ONs induce a marked increase in thermal stability, which is particularly apparent in a buffer system with a low salt concentration. The increase in thermal stability is thought to be caused, at least in part, by decreased electrostatic repulsion between the negatively charged phosphate backbones when positively charged amino acid residues are appended. Upon incorporation of more than one 2′-amino-LNA modification, the effects are found to be nearly additive. For comparison, 2′-amino-LNA derivatives modified with uncharged groups have been synthesised and their effect on duplex thermal stability likewise investigated.

Graphical abstract: Amino acids attached to 2′-amino-LNA: synthesis and excellent duplex stability

Supplementary files

Article information

Article type
Paper
Submitted
03 Aug 2010
Accepted
21 Sep 2010
First published
03 Nov 2010

Org. Biomol. Chem., 2011,9, 243-252

Amino acids attached to 2′-amino-LNA: synthesis and excellent duplex stability

M. W. Johannsen, L. Crispino, M. C. Wamberg, N. Kalra and J. Wengel, Org. Biomol. Chem., 2011, 9, 243 DOI: 10.1039/C0OB00532K

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