title: Synthesis and properties of mRNA cap analogs containing phosphorothioate moiety in 5',5'-triphosphate chain.
abstract: Nucleosides and oligonucleotides with an oxygen replaced by sulfur atom are an interesting class of compounds because of their improved stability toward enzymatic cleavage by nucleases. We have synthesized several dinucleotide mRNA cap analogs containing a phosphorothioate moiety in the alpha, beta, or gamma position of 5',5'-triphosphate chain [m7Gp(s)ppG, m7Gpp(s)pG, and m7Gppp(s)G]. These are the first examples of the biologically important 5'mRNA cap analogs containing a phosphorothioate moiety, and these compounds may be useful in a variety of biochemical and biotechnological applications. Incorporation of a sulfur atom in the alpha or gamma position within the dinucleotide cap analog was achieved using PSCl3 in a nucleoside phosphorylation reaction followed by coupling the phosphorothioate of nucleoside with a second nucleotide. Synthesis of cap analogs with the phosphorothioate moiety in beta position was performed using an organic phosphorothioate salt in a coupling reaction with an activated nucleotide. The structures of newly synthesized compounds was confirmed using MS and 1H and 31P NMR spectroscopy. We present here the results of preliminary studies on their interaction with translation initiation factor eIF4E and enzymatic hydrolysis with human and nematode DcpS scavengers.
authors.affiliation: Department of Biophysics, Institute of Experimental Physics, Warsaw University, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kowalska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lewdorowicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Zuberek
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bojarska
authors.forename: Jacek
authors.initials: J
authors.lastname: Wojcik
authors.forename: Lean S
authors.initials: LS
authors.lastname: Cohen
authors.forename: Richard E
authors.initials: RE
authors.lastname: Davis
authors.forename: Janusz
authors.initials: J
authors.lastname: Stepinski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Stolarski
authors.forename: Edward
authors.initials: E
authors.lastname: Darzynkiewicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Jemielity
mesh_terms: D000818:Animals; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D009841:Oligonucleotides / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry*; D012314:RNA Cap Analogs / Q000737:chemistry*; D012315:RNA Caps / Q000138:chemical synthesis* / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D009841:Oligonucleotides; D010710:Phosphates; D011122:Polyphosphates; D012314:RNA Cap Analogs; D012315:RNA Caps; D012333:RNA, Messenger; C005692:triphosphoric acid