Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA
DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress, and X-ray crystallography. Formacetal modifications have remarkably different effects on double helical RNA and D...
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| Veröffentlicht in: | Journal of the American Chemical Society 2009-10, Vol.131 (41), p.14932-14937 |
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| creator | Kolarovic, Andrej Schweizer, Emma Greene, Emily Gironda, Mark Pallan, Pradeep S Egli, Martin Rozners, Eriks |
| description | DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress, and X-ray crystallography. Formacetal modifications have remarkably different effects on double helical RNA and DNAthe formacetal stabilizes the RNA helix by +0.7 °C but destabilizes the DNA helix by −1.6 °C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration. A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer). Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA-based gene control strategies, such as RNA interference. |
| doi_str_mv | 10.1021/ja904926e |
| format | Article |
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Formacetal modifications have remarkably different effects on double helical RNA and DNAthe formacetal stabilizes the RNA helix by +0.7 °C but destabilizes the DNA helix by −1.6 °C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration. A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer). Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA-based gene control strategies, such as RNA interference.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja904926e</identifier><identifier>PMID: 19824732</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Acetals - chemistry ; ADENOSINE ; Circular Dichroism ; CRYSTAL STRUCTURE ; CRYSTALLOGRAPHY ; Crystallography, X-Ray ; DNA ; DNA - chemistry ; GENES ; HYDRATION ; MATERIALS SCIENCE ; MELTING ; Models, Molecular ; MODIFICATIONS ; national synchrotron light source ; Nucleic Acid Conformation ; Nucleic Acid Denaturation ; NUCLEOSIDES ; OLIGONUCLEOTIDES ; Oligonucleotides - chemistry ; Osmotic Pressure ; PHOSPHATES ; RNA ; RNA - chemistry ; RNA Stability ; STABILITY ; Temperature ; Transition Temperature ; URIDINE</subject><ispartof>Journal of the American Chemical Society, 2009-10, Vol.131 (41), p.14932-14937</ispartof><rights>Copyright © 2009 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a496t-8b65ce864badbd0e11c215f28515263543e83cbfd3aea9f6f665a0debfa537dc3</citedby><cites>FETCH-LOGICAL-a496t-8b65ce864badbd0e11c215f28515263543e83cbfd3aea9f6f665a0debfa537dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ja904926e$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ja904926e$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,776,780,881,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19824732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/980286$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Kolarovic, Andrej</creatorcontrib><creatorcontrib>Schweizer, Emma</creatorcontrib><creatorcontrib>Greene, Emily</creatorcontrib><creatorcontrib>Gironda, Mark</creatorcontrib><creatorcontrib>Pallan, Pradeep S</creatorcontrib><creatorcontrib>Egli, Martin</creatorcontrib><creatorcontrib>Rozners, Eriks</creatorcontrib><creatorcontrib>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</creatorcontrib><title>Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress, and X-ray crystallography. Formacetal modifications have remarkably different effects on double helical RNA and DNAthe formacetal stabilizes the RNA helix by +0.7 °C but destabilizes the DNA helix by −1.6 °C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration. A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer). Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA-based gene control strategies, such as RNA interference.</description><subject>Acetals - chemistry</subject><subject>ADENOSINE</subject><subject>Circular Dichroism</subject><subject>CRYSTAL STRUCTURE</subject><subject>CRYSTALLOGRAPHY</subject><subject>Crystallography, X-Ray</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>GENES</subject><subject>HYDRATION</subject><subject>MATERIALS SCIENCE</subject><subject>MELTING</subject><subject>Models, Molecular</subject><subject>MODIFICATIONS</subject><subject>national synchrotron light source</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleic Acid Denaturation</subject><subject>NUCLEOSIDES</subject><subject>OLIGONUCLEOTIDES</subject><subject>Oligonucleotides - chemistry</subject><subject>Osmotic Pressure</subject><subject>PHOSPHATES</subject><subject>RNA</subject><subject>RNA - chemistry</subject><subject>RNA Stability</subject><subject>STABILITY</subject><subject>Temperature</subject><subject>Transition Temperature</subject><subject>URIDINE</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkd-KEzEUh4Mobq1e-AISL0QEq_kzk2b2Qqir6y7sdkHrdcgkZ7YpaVKTjNA38XGNtqwKXoWcfPnOj3MQekrJG0oYfbvRHWk6JuAemtCWkVlLmbiPJoQQNptLwU_Qo5w39dowSR-iE9pJ1sw5m6Afl6FA2nm9x3HAX0oaTRkTvMYXe5t0cTFgHSxerSFtta-A7p13ZY9dwOex1gyUWr-O1g0OLL7x7jaG0XiIxVnIp_jzcoGvq34VPVQj4GUMVevM8ZP53SXj91BqElzWOuAPy8Vj9GDQPsOT4zlFX88_rs4uZlc3ny7PFlcz3XSizGQvWgNSNL22vSVAqWG0HZhs6yAEbxsOkpt-sFyD7gYxCNFqYqEfdMvn1vApenfw7sZ-C9ZAKEl7tUtuq9NeRe3Uvy_BrdVt_K6YZJx1XRU8PwhiLk5l4wqYtYkhgCmqk4TV-U_Ry2OTFL-NkIvaumzAex0gjlnNeUNk2wleyVcH0qSYc4LhLgkl6tey1d2yK_vs7-h_yON2K_DiAGiT1SaOKdRJ_kf0E0-9tGI</recordid><startdate>20091021</startdate><enddate>20091021</enddate><creator>Kolarovic, Andrej</creator><creator>Schweizer, Emma</creator><creator>Greene, Emily</creator><creator>Gironda, Mark</creator><creator>Pallan, Pradeep S</creator><creator>Egli, Martin</creator><creator>Rozners, Eriks</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>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20091021</creationdate><title>Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA</title><author>Kolarovic, Andrej ; Schweizer, Emma ; Greene, Emily ; Gironda, Mark ; Pallan, Pradeep S ; Egli, Martin ; Rozners, Eriks</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a496t-8b65ce864badbd0e11c215f28515263543e83cbfd3aea9f6f665a0debfa537dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acetals - chemistry</topic><topic>ADENOSINE</topic><topic>Circular Dichroism</topic><topic>CRYSTAL STRUCTURE</topic><topic>CRYSTALLOGRAPHY</topic><topic>Crystallography, X-Ray</topic><topic>DNA</topic><topic>DNA - chemistry</topic><topic>GENES</topic><topic>HYDRATION</topic><topic>MATERIALS SCIENCE</topic><topic>MELTING</topic><topic>Models, Molecular</topic><topic>MODIFICATIONS</topic><topic>national synchrotron light source</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleic Acid Denaturation</topic><topic>NUCLEOSIDES</topic><topic>OLIGONUCLEOTIDES</topic><topic>Oligonucleotides - chemistry</topic><topic>Osmotic Pressure</topic><topic>PHOSPHATES</topic><topic>RNA</topic><topic>RNA - chemistry</topic><topic>RNA Stability</topic><topic>STABILITY</topic><topic>Temperature</topic><topic>Transition Temperature</topic><topic>URIDINE</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kolarovic, Andrej</creatorcontrib><creatorcontrib>Schweizer, Emma</creatorcontrib><creatorcontrib>Greene, Emily</creatorcontrib><creatorcontrib>Gironda, Mark</creatorcontrib><creatorcontrib>Pallan, Pradeep S</creatorcontrib><creatorcontrib>Egli, Martin</creatorcontrib><creatorcontrib>Rozners, Eriks</creatorcontrib><creatorcontrib>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kolarovic, Andrej</au><au>Schweizer, Emma</au><au>Greene, Emily</au><au>Gironda, Mark</au><au>Pallan, Pradeep S</au><au>Egli, Martin</au><au>Rozners, Eriks</au><aucorp>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2009-10-21</date><risdate>2009</risdate><volume>131</volume><issue>41</issue><spage>14932</spage><epage>14937</epage><pages>14932-14937</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress, and X-ray crystallography. Formacetal modifications have remarkably different effects on double helical RNA and DNAthe formacetal stabilizes the RNA helix by +0.7 °C but destabilizes the DNA helix by −1.6 °C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration. A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer). Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA-based gene control strategies, such as RNA interference.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>19824732</pmid><doi>10.1021/ja904926e</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetals - chemistry ADENOSINE Circular Dichroism CRYSTAL STRUCTURE CRYSTALLOGRAPHY Crystallography, X-Ray DNA DNA - chemistry GENES HYDRATION MATERIALS SCIENCE MELTING Models, Molecular MODIFICATIONS national synchrotron light source Nucleic Acid Conformation Nucleic Acid Denaturation NUCLEOSIDES OLIGONUCLEOTIDES Oligonucleotides - chemistry Osmotic Pressure PHOSPHATES RNA RNA - chemistry RNA Stability STABILITY Temperature Transition Temperature URIDINE |
| title | Interplay of Structure, Hydration and Thermal Stability in Formacetal Modified Oligonucleotides: RNA May Tolerate Nonionic Modifications Better than DNA |
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