Lingala Suresh, Nordstrøm Lars Ulrik, Mallikaratchy Prabodhika R
Department of Chemistry, Lehman College, The City University of New York, 250 Bedford Park Blvd. West, Bronx, NY 10468, USA.
Department of Biochemistry and Chemical Synthesis Core Facility, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461 Bronx, NY, USA.
Tetrahedron Lett. 2019 Jan 17;60(3):211-213. doi: 10.1016/j.tetlet.2018.12.018. Epub 2018 Dec 8.
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 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.
铜催化的叠氮化物-炔烃环加成（CuAAC）化学用于交联和稳定寡核苷酸的应用受到叠氮化物与自动化寡核苷酸合成中使用的亚磷酰胺不相容性的限制。在此，我们报告了合成胸苷和胞苷亚磷酰胺叠氮化物衍生物的优化反应条件。在室温下使用磷核磁共振（P NMR）对新型亚磷酰胺的稳定性进行研究，结果表明6小时后降解率低于10%。叠氮化物修饰的胸苷成功地用作DNA序列标准亚磷酰胺合成中的内部修饰剂。合成的嘧啶叠氮化物和炔烃衍生物将使叠氮化物和炔烃点击对能够有效地掺入核酸中，从而拓宽点击化学在核酸化学研究中的应用范围。
