Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners
The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their development. In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemica...
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| Veröffentlicht in: | Nucleic acids research 2001-10, Vol.29 (20), p.4187-4194 |
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| creator | Van Aerschot, A Meldgaard, M Schepers, G Volders, F Rozenski, J Busson, R Herdewijn, P |
| description | The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their development. In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemical properties of their respective oligomers were evaluated. Generally, oligonucleotides (ONs) containing the 3'-O-methyl derivative 1 showed a small increase in thermal stability towards complementary sequences as compared to HNA. Compared to the altritol modification, 3'-O-methylation seems to cause a small decrease in thermal stability of duplexes, especially when targeting RNA. These results suggest the possibility of derivatisation of the 3'-hydroxyl group of altritol-containing congeners without significantly affecting the thermal stability of the duplexes. The methyl glycosidic analogues 2 likewise increased the affinity for RNA in comparison with well-known HNA, while at the same time being economically more favorable monomers. However, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to induce a beneficial pre-organised structure, the positive effect of the 3'-O-methyl derivative 1 proved larger than that of 2. |
| doi_str_mv | 10.1093/nar/29.20.4187 |
| format | Article |
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In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemical properties of their respective oligomers were evaluated. Generally, oligonucleotides (ONs) containing the 3'-O-methyl derivative 1 showed a small increase in thermal stability towards complementary sequences as compared to HNA. Compared to the altritol modification, 3'-O-methylation seems to cause a small decrease in thermal stability of duplexes, especially when targeting RNA. These results suggest the possibility of derivatisation of the 3'-hydroxyl group of altritol-containing congeners without significantly affecting the thermal stability of the duplexes. The methyl glycosidic analogues 2 likewise increased the affinity for RNA in comparison with well-known HNA, while at the same time being economically more favorable monomers. However, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to induce a beneficial pre-organised structure, the positive effect of the 3'-O-methyl derivative 1 proved larger than that of 2.</description><identifier>ISSN: 1362-4962</identifier><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/29.20.4187</identifier><identifier>PMID: 11600707</identifier><identifier>CODEN: NARHAD</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Methylation ; Nucleic Acid Hybridization - methods ; nucleoside analogues ; Oligonucleotides, Antisense - chemical synthesis ; Oligonucleotides, Antisense - chemistry ; Oligonucleotides, Antisense - metabolism ; Polyribonucleotides - metabolism ; RNA - metabolism ; RNA Stability ; Sugar Alcohols - metabolism</subject><ispartof>Nucleic acids research, 2001-10, Vol.29 (20), p.4187-4194</ispartof><rights>Copyright Oxford University Press(England) Oct 15, 2001</rights><rights>Copyright © 2001 Oxford University Press 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-83f3e2d0d07c17dfcd81463c93ea8bd41b9351e51507feb694af5db660c3bc3b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC60215/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC60215/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11600707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Aerschot, A</creatorcontrib><creatorcontrib>Meldgaard, M</creatorcontrib><creatorcontrib>Schepers, G</creatorcontrib><creatorcontrib>Volders, F</creatorcontrib><creatorcontrib>Rozenski, J</creatorcontrib><creatorcontrib>Busson, R</creatorcontrib><creatorcontrib>Herdewijn, P</creatorcontrib><title>Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their development. In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemical properties of their respective oligomers were evaluated. Generally, oligonucleotides (ONs) containing the 3'-O-methyl derivative 1 showed a small increase in thermal stability towards complementary sequences as compared to HNA. Compared to the altritol modification, 3'-O-methylation seems to cause a small decrease in thermal stability of duplexes, especially when targeting RNA. These results suggest the possibility of derivatisation of the 3'-hydroxyl group of altritol-containing congeners without significantly affecting the thermal stability of the duplexes. The methyl glycosidic analogues 2 likewise increased the affinity for RNA in comparison with well-known HNA, while at the same time being economically more favorable monomers. However, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to induce a beneficial pre-organised structure, the positive effect of the 3'-O-methyl derivative 1 proved larger than that of 2.</description><subject>Methylation</subject><subject>Nucleic Acid Hybridization - methods</subject><subject>nucleoside analogues</subject><subject>Oligonucleotides, Antisense - chemical synthesis</subject><subject>Oligonucleotides, Antisense - chemistry</subject><subject>Oligonucleotides, Antisense - metabolism</subject><subject>Polyribonucleotides - metabolism</subject><subject>RNA - metabolism</subject><subject>RNA Stability</subject><subject>Sugar Alcohols - metabolism</subject><issn>1362-4962</issn><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFDEUx4MotlavHmXw4G22-Z0JeJGitVDoRc8hk2R2UjLJmmRK9783yy61ehECCbzP5_FevgC8R3CDoCSXUedLLDcYbigaxAtwjgjHPZUcv3z2PgNvSrmHEFHE6GtwhhCHUEBxDnY3yy6nB2e7eT9mb33R1afY7VJ1sXodujR1KfhtiqsJLlVvXelMapYvPm67u35xdd4HXVsPHee9zWl2j76m0B2V0pRmxK2LLpe34NWkQ3HvTvcF-Pnt64-r7_3t3fXN1Zfb3lCKaz-QiThsoYXCIGEnYwdEOTGSOD2MlqJREoYcQwyKyY1cUj0xO3IODRnbIRfg87Hvbh0XZ03bJuug2tiLznuVtFd_V6Kf1TY9KA4xYk3_dNJz-rW6UtXii3Eh6OjSWpTASDLOyH9BNGAmBUcN_PgPeJ_WHNsfKAwhE4SQA7Q5QianUrKbngZGUB0CVy1whWVT1CHwJnx4vuYf_JQw-Q1uWau1</recordid><startdate>20011015</startdate><enddate>20011015</enddate><creator>Van Aerschot, A</creator><creator>Meldgaard, M</creator><creator>Schepers, G</creator><creator>Volders, F</creator><creator>Rozenski, J</creator><creator>Busson, R</creator><creator>Herdewijn, P</creator><general>Oxford Publishing Limited (England)</general><general>Oxford University Press</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>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20011015</creationdate><title>Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners</title><author>Van Aerschot, A ; Meldgaard, M ; Schepers, G ; Volders, F ; Rozenski, J ; Busson, R ; Herdewijn, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-83f3e2d0d07c17dfcd81463c93ea8bd41b9351e51507feb694af5db660c3bc3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Methylation</topic><topic>Nucleic Acid Hybridization - methods</topic><topic>nucleoside analogues</topic><topic>Oligonucleotides, Antisense - chemical synthesis</topic><topic>Oligonucleotides, Antisense - chemistry</topic><topic>Oligonucleotides, Antisense - metabolism</topic><topic>Polyribonucleotides - metabolism</topic><topic>RNA - metabolism</topic><topic>RNA Stability</topic><topic>Sugar Alcohols - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Aerschot, A</creatorcontrib><creatorcontrib>Meldgaard, M</creatorcontrib><creatorcontrib>Schepers, G</creatorcontrib><creatorcontrib>Volders, F</creatorcontrib><creatorcontrib>Rozenski, J</creatorcontrib><creatorcontrib>Busson, R</creatorcontrib><creatorcontrib>Herdewijn, P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Aerschot, A</au><au>Meldgaard, M</au><au>Schepers, G</au><au>Volders, F</au><au>Rozenski, J</au><au>Busson, R</au><au>Herdewijn, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2001-10-15</date><risdate>2001</risdate><volume>29</volume><issue>20</issue><spage>4187</spage><epage>4194</epage><pages>4187-4194</pages><issn>1362-4962</issn><issn>0305-1048</issn><eissn>1362-4962</eissn><coden>NARHAD</coden><abstract>The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their development. In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemical properties of their respective oligomers were evaluated. Generally, oligonucleotides (ONs) containing the 3'-O-methyl derivative 1 showed a small increase in thermal stability towards complementary sequences as compared to HNA. Compared to the altritol modification, 3'-O-methylation seems to cause a small decrease in thermal stability of duplexes, especially when targeting RNA. These results suggest the possibility of derivatisation of the 3'-hydroxyl group of altritol-containing congeners without significantly affecting the thermal stability of the duplexes. The methyl glycosidic analogues 2 likewise increased the affinity for RNA in comparison with well-known HNA, while at the same time being economically more favorable monomers. However, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to induce a beneficial pre-organised structure, the positive effect of the 3'-O-methyl derivative 1 proved larger than that of 2.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>11600707</pmid><doi>10.1093/nar/29.20.4187</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Methylation Nucleic Acid Hybridization - methods nucleoside analogues Oligonucleotides, Antisense - chemical synthesis Oligonucleotides, Antisense - chemistry Oligonucleotides, Antisense - metabolism Polyribonucleotides - metabolism RNA - metabolism RNA Stability Sugar Alcohols - metabolism |
| title | Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners |
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