| pubmed-article:21299239 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21299239 | lifeskim:mentions | umls-concept:C2936295 | lld:lifeskim |
| pubmed-article:21299239 | lifeskim:mentions | umls-concept:C1099354 | lld:lifeskim |
| pubmed-article:21299239 | lifeskim:mentions | umls-concept:C1160466 | lld:lifeskim |
| pubmed-article:21299239 | lifeskim:mentions | umls-concept:C1328819 | lld:lifeskim |
| pubmed-article:21299239 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:21299239 | pubmed:dateCreated | 2011-2-25 | lld:pubmed |
| pubmed-article:21299239 | pubmed:abstractText | 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. | lld:pubmed |
| pubmed-article:21299239 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21299239 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21299239 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21299239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21299239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21299239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21299239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21299239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21299239 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21299239 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:21299239 | pubmed:issn | 1520-6904 | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:GillF TFT | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:ManoharanMuth... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:SekineMitsuoM | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:MaierMartin... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:YamadaTakeshi... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:RajeevKallant... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:MatsudaShigeo... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:AlamMd... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:CharisseKlaus... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:PengChang... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:JayaprakashK... | lld:pubmed |
| pubmed-article:21299239 | pubmed:author | pubmed-author:AddepalliHari... | lld:pubmed |
| pubmed-article:21299239 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21299239 | pubmed:day | 4 | lld:pubmed |
| pubmed-article:21299239 | pubmed:volume | 76 | lld:pubmed |
| pubmed-article:21299239 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21299239 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21299239 | pubmed:pagination | 1198-211 | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:meshHeading | pubmed-meshheading:21299239... | lld:pubmed |
| pubmed-article:21299239 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21299239 | pubmed:articleTitle | Versatile site-specific conjugation of small molecules to siRNA using click chemistry. | lld:pubmed |
| pubmed-article:21299239 | pubmed:affiliation | Drug Discovery, Alnylam Pharmaceuticals, Cambridge, Massachusetts 02142, USA. | lld:pubmed |
| pubmed-article:21299239 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21299239 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
