Synthesis and properties of mRNA cap analogs containing phosphorothioate moiety in 5',5'-triphosphate chain.
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.
Kowalska
Joanna
J
Department of Biophysics, Institute of Experimental Physics, Warsaw University, Warsaw, Poland.
Lewdorowicz
Magdalena
M
Zuberek
Joanna
J
Bojarska
Elzbieta
E
Wojcik
Jacek
J
Cohen
Lean S
LS
Davis
Richard E
RE
Stepinski
Janusz
J
Stolarski
Ryszard
R
Darzynkiewicz
Edward
E
Jemielity
Jacek
J
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
D039561:Eukaryotic Initiation Factor-4E; D009841:Oligonucleotides; D010710:Phosphates; D011122:Polyphosphates; D012314:RNA Cap Analogs; D012315:RNA Caps; D012333:RNA, Messenger; C005692:triphosphoric acid