title: A Scalable Synthesis of α-L-Threose Nucleic Acid Monomers.
abstract: Recent advances in polymerase engineering have made it possible to copy information back and forth between DNA and artificial genetic polymers composed of TNA (α-L-threofuranosyl-(3',2') nucleic acid). This property, coupled with enhanced nuclease stability relative to natural DNA and RNA, warrants further investigation into the structural and functional properties of TNA as an artificial genetic polymer for synthetic biology. Here, we report a highly optimized chemical synthesis protocol for constructing multigram quantities of TNA nucleosides that can be readily converted to nucleoside 2'-phosphoramidites or 3'-triphosphates for solid-phase and polymerase-mediated synthesis, respectively. The synthetic protocol involves 10 chemical transformations with three crystallization steps and a single chromatographic purification, which results in an overall yield of 16-23% depending on the identity of the nucleoside (A, C, G, T).
authors.affiliation: Department of Pharmaceutical Sciences, University of California , Irvine, California 92697, United States.
authors.forename: Sujay P
authors.initials: SP
authors.lastname: Sau
authors.affiliation: The Biodesign Institute, Arizona State University , Tempe, Arizona 85287-5301, United States.
authors.forename: Nour Eddine
authors.initials: NE
authors.lastname: Fahmi
authors.affiliation: Department of Pharmaceutical Sciences, University of California , Irvine, California 92697, United States.
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Liao
authors.affiliation: Department of Pharmaceutical Sciences, University of California , Irvine, California 92697, United States.
authors.forename: Saikat
authors.initials: S
authors.lastname: Bala
authors.affiliation: Department of Pharmaceutical Sciences, University of California , Irvine, California 92697, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Chaput
mesh_terms: D004247:DNA / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism; D009696:Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D009705:Nucleosides / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013780:Tetroses / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D009696:Nucleic Acids; D009705:Nucleosides; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D013780:Tetroses; C434331:phosphoramidite; D004247:DNA; D004259:DNA-Directed DNA Polymerase; C073321:erythrose