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Tetrahedron Lett. 2019 Jan 17;60(3):211-213. doi: 10.1016/j.tetlet.2018.12.018. Epub 2018 Dec 8.

Synthesis of stable azide and alkyne functionalized phosphoramidite nucleosides.

Author information

1
Department of Chemistry, Lehman College, The City University of New York, 250 Bedford Park Blvd. West, Bronx, NY 10468, USA.
2
Department of Biochemistry and Chemical Synthesis Core Facility, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461 Bronx, NY, USA.
3
Ph.D. Program in Chemistry and Biochemistry, CUNY Graduate Center, 365 Fifth Avenue, New York, NY 10016, USA.
4
Ph.D. Program in Molecular, Cellular and Developmental Biology, CUNY Graduate Center, 365 Fifth Avenue, New York, NY 10016, USA.

Abstract

The use of CuAAC chemistry to crosslink and stabilize oligonucleotides has been limited by the incompatibility of azides with the phosphoramidites used in automated oligonucleotide synthesis. Herein we report optimized reaction conditions to synthesize azide derivatives of thymidine and cytidine phosphoramidites. Investigation of the stability of the novel phosphoramidites using 31P NMR at room temperature showed less than 10% degradation after 6 hours. The azide modified thymidine was successfully utilized as an internal modifier in the standard phosphoramidite synthesis of a DNA sequence. The synthesized azide and alkyne derivatives of pyrimidines will allow efficient incorporation of azide and alkyne click pairs into nucleic acids, thus widening the applicability of click chemistry in investigating the chemistry of nucleic acids.

KEYWORDS:

Chemical biology; Click Chemistry; CuAAC; Oligonucleotide synthesis; Phosphoramidites

PMID:
30804607
PMCID:
PMC6386463
[Available on 2020-01-17]
DOI:
10.1016/j.tetlet.2018.12.018

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