Post-Synthetic Modification of Oligonucleotides via Orthogonal Amidation and Copper Catalyzed Cycloaddition Reactions
An efficient multicomponent orthogonal protocol was developed for post-synthetic oligonucleotide modification using commercially available 2′-O-methyl ester and 2′-O-propargyl nucleoside scaffolds. Amidation of methyl esters with primary amines was achieved in the presence of 2′-propargyl groups whi...
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| Veröffentlicht in: | Bioconjugate chemistry 2018-06, Vol.29 (6), p.1859-1865 |
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| container_issue | 6 |
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| container_title | Bioconjugate chemistry |
| container_volume | 29 |
| creator | Zewge, Daniel Butora, Gabor Sherer, Edward C Tellers, David M Sidler, Daniel R Gouker, Joseph Copeland, Greg Jadhav, Vasant Li, Zhen Armstrong, Joseph Davies, Ian W |
| description | An efficient multicomponent orthogonal protocol was developed for post-synthetic oligonucleotide modification using commercially available 2′-O-methyl ester and 2′-O-propargyl nucleoside scaffolds. Amidation of methyl esters with primary amines was achieved in the presence of 2′-propargyl groups which were utilized for subsequent copper catalyzed cycloaddition with GalNAc-azide. The methodology was applied to generate siRNA composed of multiple amide and triazole conjugates. Computational methods were used to illustrate the impact of substitution at the 2′-position. This a powerful post-oligomerization technique for rapidly introducing diversity to oligonucleotide design. |
| doi_str_mv | 10.1021/acs.bioconjchem.8b00298 |
| format | Article |
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Amidation of methyl esters with primary amines was achieved in the presence of 2′-propargyl groups which were utilized for subsequent copper catalyzed cycloaddition with GalNAc-azide. The methodology was applied to generate siRNA composed of multiple amide and triazole conjugates. Computational methods were used to illustrate the impact of substitution at the 2′-position. 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This a powerful post-oligomerization technique for rapidly introducing diversity to oligonucleotide design.</description><subject>Acetylgalactosamine - chemical synthesis</subject><subject>Acetylgalactosamine - chemistry</subject><subject>Amides - chemical synthesis</subject><subject>Amides - chemistry</subject><subject>Amines</subject><subject>Azides - chemical synthesis</subject><subject>Azides - chemistry</subject><subject>Catalysis</subject><subject>Chemical reactions</subject><subject>Click Chemistry - methods</subject><subject>Computer applications</subject><subject>Copper</subject><subject>Copper - chemistry</subject><subject>Cycloaddition</subject><subject>Cycloaddition Reaction - methods</subject><subject>Efficiency</subject><subject>Esterification</subject><subject>Esters</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Oligomerization</subject><subject>Oligonucleotides</subject><subject>Oligonucleotides - chemical synthesis</subject><subject>Oligonucleotides - chemistry</subject><subject>Propargyl groups</subject><subject>Protocol</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Small Interfering - chemical synthesis</subject><subject>RNA, Small Interfering - chemistry</subject><subject>siRNA</subject><subject>Studies</subject><subject>Triazoles - chemical synthesis</subject><subject>Triazoles - chemistry</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1r2zAUhsVYabq0f2Ez7KY3TvUZS5chdN0gJaVbr82xJC8KtpVZ8iD99ZWbLIzeFA6cw-E5rxAPQl8InhFMyQ3oMKuc177b6o1tZ7LCmCr5AV0QQXHOJaEf04w5y4nEdII-hbDFGCsi6TmaJFQxIdgFGh58iPnPfRc3Njqd3XvjaqchOt9lvs7Wjfvtu0E31kdnbMj-OsjWfdz4tIYmW7TOHGDoTLb0u53tsyVEaPbPNi32uvFgjHtFHi3ocQiX6KyGJtirY5-ip2-3v5bf89X67sdyscqBSRFzNde2EqygoEjFCjVnjBEqIVVFgEChsOKCGzCMG6K5oDWX2nACghEmKjZF14fcXe__DDbEsnVB26aBzvohlBQLrigZk6fo6xt064c-fXGkClrMJWY0UcWB0r0Pobd1uetdC_2-JLgczZTJTPmfmfJoJl1-PuYPVWvN6e6figSwAzAmnN5-L_YF4eOg8Q</recordid><startdate>20180620</startdate><enddate>20180620</enddate><creator>Zewge, Daniel</creator><creator>Butora, Gabor</creator><creator>Sherer, Edward C</creator><creator>Tellers, David M</creator><creator>Sidler, Daniel R</creator><creator>Gouker, Joseph</creator><creator>Copeland, Greg</creator><creator>Jadhav, Vasant</creator><creator>Li, Zhen</creator><creator>Armstrong, Joseph</creator><creator>Davies, Ian W</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8178-9186</orcidid><orcidid>https://orcid.org/0000-0003-3638-0984</orcidid></search><sort><creationdate>20180620</creationdate><title>Post-Synthetic Modification of Oligonucleotides via Orthogonal Amidation and Copper Catalyzed Cycloaddition Reactions</title><author>Zewge, Daniel ; 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| ispartof | Bioconjugate chemistry, 2018-06, Vol.29 (6), p.1859-1865 |
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| source | MEDLINE; ACS Publications |
| subjects | Acetylgalactosamine - chemical synthesis Acetylgalactosamine - chemistry Amides - chemical synthesis Amides - chemistry Amines Azides - chemical synthesis Azides - chemistry Catalysis Chemical reactions Click Chemistry - methods Computer applications Copper Copper - chemistry Cycloaddition Cycloaddition Reaction - methods Efficiency Esterification Esters HeLa Cells Humans Models, Molecular Oligomerization Oligonucleotides Oligonucleotides - chemical synthesis Oligonucleotides - chemistry Propargyl groups Protocol Ribonucleic acid RNA RNA, Small Interfering - chemical synthesis RNA, Small Interfering - chemistry siRNA Studies Triazoles - chemical synthesis Triazoles - chemistry |
| title | Post-Synthetic Modification of Oligonucleotides via Orthogonal Amidation and Copper Catalyzed Cycloaddition Reactions |
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