Oligodeoxynucleotides containing 2'-amino-LNA nucleotides as constrained morpholino phosphoramidate and phosphorodiamidate monomers

Kim Vejlegaard; Sibasish Paul; Tamer Kosbar; Jesper Wengel; Marvin H Caruthers

doi:10.1016/j.bmcl.2017.05.023

Oligodeoxynucleotides containing 2'-amino-LNA nucleotides as constrained morpholino phosphoramidate and phosphorodiamidate monomers

Bioorg Med Chem Lett. 2017 Jul 15;27(14):3173-3176. doi: 10.1016/j.bmcl.2017.05.023. Epub 2017 May 17.

Authors

Kim Vejlegaard¹, Sibasish Paul², Tamer Kosbar³, Jesper Wengel⁴, Marvin H Caruthers²

Affiliations

¹ Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
² Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA.
³ Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark; Department of Chemistry, Faculty of Science, Damietta University, New Damietta 34517, Egypt.
⁴ Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: jwe@sdu.dk.

PMID: 28552336
DOI: 10.1016/j.bmcl.2017.05.023

Abstract

Incorporation in a 2'→5' direction of a phosphorodiamidite 2'-amino-LNA-T nucleotide as the morpholino phosphoramidate and N,N-dimethylamino phosphorodiamidate monomers into six oligonucleotides is reported. Thermal denaturation studies showed that the novel 2'-amino-LNA-based morpholino monomers exert a destabilizing effects on duplexes formed with complementary DNA and RNA.

Keywords: 2′-Amino-LNA; Morpholino; Oligonucleotide synthesis; Phosphordiamidite.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemistry*
DNA / chemistry
DNA / metabolism
Molecular Dynamics Simulation
Morpholinos / chemistry*
Morpholinos / metabolism
Nucleic Acid Conformation
Nucleic Acid Denaturation
Oligodeoxyribonucleotides / chemistry*
Oligodeoxyribonucleotides / metabolism
Oligonucleotides / chemistry*
Phosphoric Acids / chemistry*
Transition Temperature

Substances

Amides
Morpholinos
Oligodeoxyribonucleotides
Oligonucleotides
Phosphoric Acids
amino-LNA
DNA
phosphoramidic acid