Synthesis and biochemical properties of novel mRNA 5' cap analogs resistant to enzymatic hydrolysis.
A series of new dinucleotide cap analogs with methylene groups replacing oxygens within the pyrophosphate moieties have been synthesized. All the compounds were resistant to the human scavenger decapping hydrolase, DcpS. Binding constants of the modified caps to eIF4E are comparable to those obtained for m7GpppG. This suggests these methylene modifications in the pyrophosphate chain do not significantly affect cap-binding at least for eIF4E. These cap analogs are also good inhibitors of in vitro translation. mRNAs capped with novel analogs were translated similarly to the mRNA capped with the parent m7GpppG.
Kalek
Marcin
M
Department of Biophysics, Institute of Experimental Physics, Warsaw University, 02-089 Warsaw, Poland.
Jemielity
Jacek
J
Grudzien
Ewa
E
Zuberek
Joanna
J
Bojarska
Elzbieta
E
Cohen
Lean S
LS
Stepinski
Janusz
J
Stolarski
Ryszard
R
Davis
Richard E
RE
Rhoads
Robert E
RE
Darzynkiewicz
Edward
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives; D008956:Models, Chemical; D009348:Nematoda; D063065:Organophosphonates / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D012314:RNA Cap Analogs; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization
D039561:Eukaryotic Initiation Factor-4E; D006838:Hydrocarbons; D063065:Organophosphonates; D012314:RNA Cap Analogs; D012333:RNA, Messenger; C030011:carbene; D008697:Methane; D010100:Oxygen