C - Chemistry – Metallurgy – 07 – H
Patent
C - Chemistry, Metallurgy
07
H
C07H 19/207 (2006.01)
Patent
CA 2692906
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.
L'invention concerne de nouveaux analogues de coiffe d'ARN comprenant un ou plusieurs groupes phosphorothioate. Les analogues peuvent également contenir des modifications en position 2'-O de la 7-méthylguanosine qui les empêchent d'être incorporés dans l'orientation inverse pendant une synthèse in vitro de l'ARNm et constituent ainsi des = analogues de coiffe anti-inverse = (ARCA). La modification d'ARCA garantit que l'atome S est positionné précisément dans les sites actifs des protéines de liaison à la coiffe dans la machinerie de traduction et de décoiffage. Les nouveaux analogues S-ARCA sont résistants aux enzymes de décoiffage in vivo. Certains S-ARCA ont une affinité pour eIF4E plus élevée que les analogues correspondants ne contenant pas un groupe phosphorothioate. Lorsque des ARNm contenant divers S-ARCA sont introduits dans des cellules mises en culture, certains sont traduits jusqu'à cinq fois plus efficacement que les ARNm synthétisés avec l'analogue classique m7GpppG.
Darzynkiewicz Edward
Grudzien-Nogalska Ewa M.
Jemielity Jacek
Kowalska Joanna
Rhoads Robert E.
Board Of Supervisors Of Louisiana State University And Agricultu
Mcfadden Fincham
University Of Warsaw
LandOfFree
Synthesis and use of anti-reverse phosphorothioate analogs... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Synthesis and use of anti-reverse phosphorothioate analogs..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Synthesis and use of anti-reverse phosphorothioate analogs... will most certainly appreciate the feedback.
Profile ID: LFCA-PAI-O-1943252