New light labile linker for solid phase synthesis of 2′- O-acetalester oligonucleotides and applications to siRNA prodrug development
A novel light labile linker for RNA synthesis was developed and used in the synthesis of acetalester conjugates. We report on the synthesis and properties of oligonucleotides containing 2′- O-(levulinic acid) and 2′- O-(amino acid) acetalesters. Given that esters serve as promoieties in several ther...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2011-06, Vol.21 (12), p.3721-3725 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Johnsson, Richard Lackey, Jeremy G. Bogojeski, Jovanka J. Damha, Masad J. |
| description | A novel light labile linker for RNA synthesis was developed and used in the synthesis of acetalester conjugates.
We report on the synthesis and properties of oligonucleotides containing 2′-
O-(levulinic acid) and 2′-
O-(amino acid) acetalesters. Given that esters serve as promoieties in several therapeutic prodrugs, we believe that these derivatives will have potential use as nucleic acid prodrugs. In addition, we report on the synthesis of a novel solid support with a photolabile linker that not only allows for the synthesis of oligonucleotides containing various 2′-
O-acetalesters, but can be generally adopted to the synthesis of base-sensitive oligoribonucleotides. The release of oligonucleotides from this support is faster than with conventional linkers. |
| doi_str_mv | 10.1016/j.bmcl.2011.04.073 |
| format | Article |
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We report on the synthesis and properties of oligonucleotides containing 2′-
O-(levulinic acid) and 2′-
O-(amino acid) acetalesters. Given that esters serve as promoieties in several therapeutic prodrugs, we believe that these derivatives will have potential use as nucleic acid prodrugs. In addition, we report on the synthesis of a novel solid support with a photolabile linker that not only allows for the synthesis of oligonucleotides containing various 2′-
O-acetalesters, but can be generally adopted to the synthesis of base-sensitive oligoribonucleotides. The release of oligonucleotides from this support is faster than with conventional linkers.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2011.04.073</identifier><identifier>PMID: 21570286</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Acetals - chemical synthesis ; Acetals - chemistry ; amino acids ; Analytical, structural and metabolic biochemistry ; Biological and medical sciences ; Carbohydrates. Nucleosides and nucleotides ; Chemistry ; Combinatorial Chemistry Techniques ; Dimerization ; esters ; Esters - chemical synthesis ; Esters - chemistry ; Exact sciences and technology ; Fundamental and applied biological sciences. Psychology ; levulinic acid ; Light ; Molecular Structure ; Nucleic acids ; Nucleic bases, nucleotides ; Nucleosides, nucleotides and oligonucleotides ; Oligonucleotides - chemical synthesis ; Oligonucleotides - chemistry ; oligoribonucleotides ; Organic chemistry ; Preparations and properties ; Prodrugs - chemical synthesis ; Prodrugs - metabolism ; RNA, Small Interfering - chemistry ; RNA, Small Interfering - metabolism ; small interfering RNA ; Temperature</subject><ispartof>Bioorganic & medicinal chemistry letters, 2011-06, Vol.21 (12), p.3721-3725</ispartof><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-603966dc1e23c1c048364c2f561087fb5e8eed8b385ce7fdc5d9c08d4354308d3</citedby><cites>FETCH-LOGICAL-c507t-603966dc1e23c1c048364c2f561087fb5e8eed8b385ce7fdc5d9c08d4354308d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2011.04.073$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24301856$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21570286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnsson, Richard</creatorcontrib><creatorcontrib>Lackey, Jeremy G.</creatorcontrib><creatorcontrib>Bogojeski, Jovanka J.</creatorcontrib><creatorcontrib>Damha, Masad J.</creatorcontrib><title>New light labile linker for solid phase synthesis of 2′- O-acetalester oligonucleotides and applications to siRNA prodrug development</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A novel light labile linker for RNA synthesis was developed and used in the synthesis of acetalester conjugates.
We report on the synthesis and properties of oligonucleotides containing 2′-
O-(levulinic acid) and 2′-
O-(amino acid) acetalesters. Given that esters serve as promoieties in several therapeutic prodrugs, we believe that these derivatives will have potential use as nucleic acid prodrugs. In addition, we report on the synthesis of a novel solid support with a photolabile linker that not only allows for the synthesis of oligonucleotides containing various 2′-
O-acetalesters, but can be generally adopted to the synthesis of base-sensitive oligoribonucleotides. The release of oligonucleotides from this support is faster than with conventional linkers.</description><subject>Acetals - chemical synthesis</subject><subject>Acetals - chemistry</subject><subject>amino acids</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Biological and medical sciences</subject><subject>Carbohydrates. Nucleosides and nucleotides</subject><subject>Chemistry</subject><subject>Combinatorial Chemistry Techniques</subject><subject>Dimerization</subject><subject>esters</subject><subject>Esters - chemical synthesis</subject><subject>Esters - chemistry</subject><subject>Exact sciences and technology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>levulinic acid</subject><subject>Light</subject><subject>Molecular Structure</subject><subject>Nucleic acids</subject><subject>Nucleic bases, nucleotides</subject><subject>Nucleosides, nucleotides and oligonucleotides</subject><subject>Oligonucleotides - chemical synthesis</subject><subject>Oligonucleotides - chemistry</subject><subject>oligoribonucleotides</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - metabolism</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA, Small Interfering - metabolism</subject><subject>small interfering RNA</subject><subject>Temperature</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcuKFDEUhgtRnHb0BVxoNuKqylyrUuBmGLzBMAPqgLuQSk51p01XyiQ1Mjt3vo-P5JOYplvdiatD4PtP_uSrqscENwST9sW2GXbGNxQT0mDe4I7dqVaEt7xmHIu71Qr3La5lzz-dVA9S2mJMOOb8fnVCiegwle2q-n4JX5F3601GXg_OQzlMnyGiMUSUgncWzRudAKXbKW8guYTCiOjPbz9qdFVrA1l7SLkECrsO02I8hOwsJKQni_Q8e2d0dmFKKAeU3PvLMzTHYOOyRhZuwId5B1N-WN0btU_w6DhPq-vXrz6ev60vrt68Oz-7qI3AXa5bzPq2tYYAZYYYzCVruaGjaAmW3TgIkABWDkwKA91ojbC9wdJyJjgrk51Wzw97S4cvS2mudi4Z8F5PEJakZMdJTyRn_0Fi2lPO-kLSA2liSCnCqObodjreKoLV3pTaqr0ptTelMFfFVAk9Oa5fhh3YP5Hfagrw7AjoZLQfo56MS3-58h4ixZ57euBGHZRex8Jcfyg3iaKb8Z52hXh5IKB87I2DqJJxMBmwLoLJygb3r6a_AJHvvQ4</recordid><startdate>20110615</startdate><enddate>20110615</enddate><creator>Johnsson, Richard</creator><creator>Lackey, Jeremy G.</creator><creator>Bogojeski, Jovanka J.</creator><creator>Damha, Masad J.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110615</creationdate><title>New light labile linker for solid phase synthesis of 2′- O-acetalester oligonucleotides and applications to siRNA prodrug development</title><author>Johnsson, Richard ; Lackey, Jeremy G. ; Bogojeski, Jovanka J. ; Damha, Masad J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-603966dc1e23c1c048364c2f561087fb5e8eed8b385ce7fdc5d9c08d4354308d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acetals - chemical synthesis</topic><topic>Acetals - chemistry</topic><topic>amino acids</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Biological and medical sciences</topic><topic>Carbohydrates. Nucleosides and nucleotides</topic><topic>Chemistry</topic><topic>Combinatorial Chemistry Techniques</topic><topic>Dimerization</topic><topic>esters</topic><topic>Esters - chemical synthesis</topic><topic>Esters - chemistry</topic><topic>Exact sciences and technology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>levulinic acid</topic><topic>Light</topic><topic>Molecular Structure</topic><topic>Nucleic acids</topic><topic>Nucleic bases, nucleotides</topic><topic>Nucleosides, nucleotides and oligonucleotides</topic><topic>Oligonucleotides - chemical synthesis</topic><topic>Oligonucleotides - chemistry</topic><topic>oligoribonucleotides</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Prodrugs - chemical synthesis</topic><topic>Prodrugs - metabolism</topic><topic>RNA, Small Interfering - chemistry</topic><topic>RNA, Small Interfering - metabolism</topic><topic>small interfering RNA</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Johnsson, Richard</creatorcontrib><creatorcontrib>Lackey, Jeremy G.</creatorcontrib><creatorcontrib>Bogojeski, Jovanka J.</creatorcontrib><creatorcontrib>Damha, Masad J.</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><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>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Johnsson, Richard</au><au>Lackey, Jeremy G.</au><au>Bogojeski, Jovanka J.</au><au>Damha, Masad J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New light labile linker for solid phase synthesis of 2′- O-acetalester oligonucleotides and applications to siRNA prodrug development</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2011-06-15</date><risdate>2011</risdate><volume>21</volume><issue>12</issue><spage>3721</spage><epage>3725</epage><pages>3721-3725</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A novel light labile linker for RNA synthesis was developed and used in the synthesis of acetalester conjugates.
We report on the synthesis and properties of oligonucleotides containing 2′-
O-(levulinic acid) and 2′-
O-(amino acid) acetalesters. Given that esters serve as promoieties in several therapeutic prodrugs, we believe that these derivatives will have potential use as nucleic acid prodrugs. In addition, we report on the synthesis of a novel solid support with a photolabile linker that not only allows for the synthesis of oligonucleotides containing various 2′-
O-acetalesters, but can be generally adopted to the synthesis of base-sensitive oligoribonucleotides. The release of oligonucleotides from this support is faster than with conventional linkers.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>21570286</pmid><doi>10.1016/j.bmcl.2011.04.073</doi><tpages>5</tpages></addata></record> |
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| subjects | Acetals - chemical synthesis Acetals - chemistry amino acids Analytical, structural and metabolic biochemistry Biological and medical sciences Carbohydrates. Nucleosides and nucleotides Chemistry Combinatorial Chemistry Techniques Dimerization esters Esters - chemical synthesis Esters - chemistry Exact sciences and technology Fundamental and applied biological sciences. Psychology levulinic acid Light Molecular Structure Nucleic acids Nucleic bases, nucleotides Nucleosides, nucleotides and oligonucleotides Oligonucleotides - chemical synthesis Oligonucleotides - chemistry oligoribonucleotides Organic chemistry Preparations and properties Prodrugs - chemical synthesis Prodrugs - metabolism RNA, Small Interfering - chemistry RNA, Small Interfering - metabolism small interfering RNA Temperature |
| title | New light labile linker for solid phase synthesis of 2′- O-acetalester oligonucleotides and applications to siRNA prodrug development |
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