SYNTHESIS AND USE OF ANTI-REVERSE PHOSPHOROTHIOATE ANALOGS OF THE MESSENGER RNA CAP
摘要
<p>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.</p>
申请公布号
EP2167523(A2)
申请公布日期
2010.03.31
申请号
EP20080771474
申请日期
2008.06.19
申请人
BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE;UNIVERSITY OF WARSAW
发明人
JEMIELITY, JACEK;GRUDZIEN-NOGALSKA, EWA, M.;KOWALSKA, JOANNA;DARZYNKIEWICZ, EDWARD;RHOADS, ROBERT, E.