Synthesis of N-Acetyl-D-galactosamine and Folic Acid Conjugated Ribozymes

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• 作者：Jasenka Matulic-Adamic ; Vladimir Serebryany ; Peter Haeberli ; Victor R. Mokler ; and Leonid Beigelman
• 刊名：Bioconjugate Chemistry
• 出版年：2002
• 出版时间：September 2002
• 年：2002
• 卷：13
• 期：5
• 页码：1071 - 1078
• 全文大小：126K
• 年卷期：v.13,no.5(September 2002)
• ISSN：1520-4812

文摘

To evaluate potential improvement in tissue specific targeting and cellular uptake of therapeuticribozymes, we have developed three new phosphoramidite reagents. These reagents can be used inautomated solid-phase synthesis to produce oligonucleotide conjugates containing N-acetyl-D-galactosamine (targeting hepatocytes) and folic acid (targeting tumor). N-Acetyl-D-galactosamine wasattached through a linker to both 2'-amino-2'-deoxyuridine and D-threoninol scaffolds, and theseconjugates were converted to phosphoramidite building blocks. Incorporation of a D-threoninol-basedmonomer into ribozymes provided multiply labeled ribozyme conjugates. Attachment of the fullyprotected pteroic acid to the D-threoninol-6-aminocaproyl-L-glutamic acid construct afforded the folicacid conjugate, which was converted into the phosphoramidite and incorporated onto the 5'-end ofthe ribozyme.