title: A new, but old, nucleoside analog: the first synthesis of 1-deaza-2'-deoxyguanosine and its properties as a nucleoside and as oligodeoxynucleotides.
abstract: The first synthesis of 5-amino-3-(2'-deoxy-beta-D-ribofuranosyl)imidazo[4,5-b]pyridin-7-one (1-deaza-2'-deoxyguanosine) is described. The compound was converted from the known AICA-deoxyriboside. The tautomeric structure of the base moiety was determined by theoretical calculation to be a hydroxyl form. Although the analog was found to be labile to acidic conditions, 1-deaza-2'-deoxyguanosine was successfully converted into a phosphoramidite derivative, which was incorporated into oligodeoxynucleotides by the standard phosphoramidite method. Thermal stabilities of oligodeoxynucleotides containing 1-deaza-2'-deoxyguanosine were investigated by thermal denaturing experiments. Also, a triphosphate analog of 1-deaza-2'-deoxyguanosine was synthesized for polymerase extension reactions. Single nucleotide insertion reactions using a template containing 1-deaza-2'-deoxyguanosine, as well as 1-deaza-2'-deoxyguanosine triphosphate, were performed using the Klenow fragment (exonuclease minus) polymerase and other polymerases. No hydrogen bonded base pairs, even a 1-deaza-2'-deoxyguanosine:cytidine base pair, were indicated by thermal denaturing studies. However, though less selective and less effective than the natural guanosine counterpart, the polymerase extension reactions suggested the formation of a base pair of 1-deaza-2'-deoxyguanosine with cytidine during the insertion reactions.
authors.affiliation: Institute for Biological Resources and Functions, Sapporo, Japan. naoshi-kojima@aist.go.jp
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kojima
authors.forename: Kaori
authors.initials: K
authors.lastname: Inoue
authors.forename: Rina
authors.initials: R
authors.lastname: Nakajima-Shibata
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Kawahara
authors.forename: Eiko
authors.initials: E
authors.lastname: Ohtsuka
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D003562:Cytidine / Q000737:chemistry; D004256:DNA Polymerase I / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009711:Nucleotides / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013698:Templates, Genetic; D013816:Thermodynamics
chemical_list: C480034:1-deaza-2'-deoxyguanosine; D009711:Nucleotides; D009838:Oligodeoxyribonucleotides; D003562:Cytidine; D004256:DNA Polymerase I; D003849:Deoxyguanosine