title: Design, synthesis and biological evaluation of dinucleotide mRNA cap analog containing propargyl moiety.
abstract: The first example of the synthesis of new dinucleotide cap analog containing propargyl group such as m(7,3'-O-propargyl)G[5']ppp[5']G is reported. The effect of propargyl cap analog with standard cap was evaluated with respect to their capping efficiency, in vitro T7 RNA polymerase transcription efficiency, and translation activity using cultured HeLa cells. It is noteworthy that propargyl cap analog outperforms standard cap by 3.1 fold in terms of translational properties. The propargyl cap analog forms a more stable complex with translation initiation factor eIF4E based on the molecular modeling studies.
authors.affiliation: Life Sciences Solutions Group, Thermo Fisher Scientific, 2130 Woodward Street, Austin, TX 78744-1832, USA.
authors.forename: Muthian
authors.initials: M
authors.lastname: Shanmugasundaram
authors.affiliation: Life Sciences Solutions Group, Thermo Fisher Scientific, 2130 Woodward Street, Austin, TX 78744-1832, USA.
authors.forename: Irudaya
authors.initials: I
authors.lastname: Charles
authors.affiliation: Life Sciences Solutions Group, Thermo Fisher Scientific, 2130 Woodward Street, Austin, TX 78744-1832, USA. Electronic address: anil.kore@thermofisher.com.
authors.forename: Anilkumar R
authors.initials: AR
authors.lastname: Kore
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry* / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D012314:RNA Cap Analogs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D015226:Dinucleoside Phosphates; D039561:Eukaryotic Initiation Factor-4E; D012314:RNA Cap Analogs; D014764:Viral Proteins; D006151:Guanosine; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases
keywords: 5′-Capped RNA; Capping efficiency; HeLa cells; In vitro transcription; Propargyl substituted cap analog; Translation efficiency