Jacek Jemielity;Joanna Kowalska;Ewa M. Grudzien-Nogalska;Edward Darzynkiewicz;Robert E. Rhoads
发明人:
Jacek Jemielity,Ewa M. Grudzien-Nogalska,Joanna Kowalska,Edward Darzynkiewicz,Robert E. Rhoads
申请号：
US12280282
公开号：
US08153773B2
申请日:
2008.06.19
申请国别(地区):
US
年份:
2012
代理人:
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.
