860640-63-7Relevant academic research and scientific papers
Cross-linked DNA: Propargylated ribonucleosides as "click" ligation sites for bifunctional azides
Pujari, Suresh S.,Seela, Frank
supporting information; scheme or table, p. 4460 - 4465 (2012/06/30)
2′-O or 3′-O-propargylated adenosines and ribothymidines were used as click targets for cross-linking of oligonucleotides with aliphatic and aromatic azides. The cross-link generates a sugar modification at the 2′-O-ligation site. Inexpensive ribonucleosi
Versatile site-specific conjugation of small molecules to siRNA using click chemistry
Yamada, Takeshi,Peng, Chang Geng,Matsuda, Shigeo,Addepalli, Haripriya,Jayaprakash, K. Narayanannair,Alam, Md. Rowshon,Mills, Kathy,Maier, Martin A.,Charisse, Klaus,Sekine, Mitsuo,Manoharan, Muthiah,Rajeev, Kallanthottathil G.
, p. 1198 - 1211 (2011/04/26)
We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and completely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5′-alkyne moieties were used for conjugation to the 5′-end of the oligonucleotide. Previously described 2′-and 3′-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3′ and 5′ termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.(Figure Presented)
