发明名称 |
SYNTHESIS AND USE OF ANTI-REVERSE PHOSPHOROTHIOATE ANALOGS OF THE MESSENGER RNA CAP |
摘要 |
New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2′-O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are“anti-reverse cap analogs”(ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five-fold more efficiently than mRNAs synthesized with the conventional analog m7GpppG. |
申请公布号 |
PT2167523(E) |
申请公布日期 |
2014.09.22 |
申请号 |
PT20080771474T |
申请日期 |
2008.06.19 |
申请人 |
BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE |
发明人 |
JACEK JEMIELITY;EWA M. GRUDZIEN-NOGALSKA;JOANNA KOWALSKA;EDWARD DARZYNKIEWICZ;ROBERT E. RHOADS |
分类号 |
C07H19/207 |
主分类号 |
C07H19/207 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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