title: Synthesis and biochemical properties of novel mRNA 5' cap analogs resistant to enzymatic hydrolysis.
abstract: 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.
authors.affiliation: Department of Biophysics, Institute of Experimental Physics, Warsaw University, 02-089 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kalek
authors.forename: Jacek
authors.initials: J
authors.lastname: Jemielity
authors.forename: Ewa
authors.initials: E
authors.lastname: Grudzien
authors.forename: Joanna
authors.initials: J
authors.lastname: Zuberek
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bojarska
authors.forename: Lean S
authors.initials: LS
authors.lastname: Cohen
authors.forename: Janusz
authors.initials: J
authors.lastname: Stepinski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Stolarski
authors.forename: Richard E
authors.initials: RE
authors.lastname: Davis
authors.forename: Robert E
authors.initials: RE
authors.lastname: Rhoads
authors.forename: Edward
authors.initials: E
authors.lastname: Darzynkiewicz
mesh_terms: 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
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D006838:Hydrocarbons; D063065:Organophosphonates; D012314:RNA Cap Analogs; D012333:RNA, Messenger; C030011:carbene; D008697:Methane; D010100:Oxygen