Synthesis of stable azide and alkyne functionalized phosphoramidite nucleosides

TETRAHEDRON LETTERS

卷:60

Article

Lingala, Suresh¹  Nordstrom, Lars Ulrik^2,3  Mallikaratchy, Prabodhika R.^1,4,5 

[1] CUNY, Lehman Coll, Dept Chem, 250 Bedford Pk Blvd W, Bronx, NY 10468 USA

[2] Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[3] Albert Einstein Coll Med, Chem Synth Core Facil, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[4] CUNY, Grad Ctr, PhD Program Chem & Biochem, 365 Fifth Ave, New York, NY 10016 USA

[5] CUNY, Grad Ctr, PhD Program Mol Cellular & Dev Biol, 365 Fifth Ave, New York, NY 10016 USA

关键词: Phosphoramidites;    Oligonucleotide synthesis;    Click chemistry;    CuAAC;    Chemical biology;   

DOI  :  10.1016/j.tetlet.2018.12.018

来源: Elsevier

【 摘 要 】

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 P-31 NMR at room temperature showed less than 10% degradation after 6 h. 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. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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