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SYNTHESIS AND USE OF A NTI-REVERSE PHOSPHOROTHIOATE ANALOGS OF THE MESSENGER RNA CAP
SYNTHESIS AND USE OF A NTI-REVERSE PHOSPHOROTHIOATE ANALOGS OF THE MESSENGER RNA CAP
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机译:信使RNA帽的NTI逆磷酸酯类似物的合成和使用
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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 m7 GpppG.
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