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
HRP20140771(T1)
申请公布日期
2014.11.07
申请号
HR2014P000771T
申请日期
2014.08.18
申请人
BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE;UNIWERSYTET WARSZAWSKI
发明人
JEMIELITY, JACEK;GRUDZIEN-NOGALSKA, EWA M.;KOWALSKA, JOANNA;DARZYNKIEWICZ, EDWARD;RHOADS, ROBERT E.