title: A new method for the synthesis of oligodeoxyribonucleotides containing 4-N-alkoxycarbonyldeoxycytidine derivatives and their hybridization properties.
abstract: Oligodeoxyribonucleotides incorporating 4-N-alkoxycarbonyldeoxycytidine derivatives were synthesized on polystyrene-type ArgoPore resins having a new benzyloxy(diisopropyl)silyl linker, by use of ZnBr(2) as the detritylating agent. The first 3'-terminal thymidine could be attached to the resin by successive in situ reactions of 5'-O-DMTr-thymidine with diisopropylsilanediyl ditriflate and an ArgoPore resin containing hydroxyl groups. The use of this new silanediyl-type linker allowed release of the DNA chain from the resin by treatment with TBAF under neutral conditions. The T(m) experiments apparently showed that incorporation of 4-N-alkoxycarbonyldeoxycytidines into DNA strands resulted in higher hybridization affinity with the complementary DNA strands than that of 4-N-acyldeoxycytidines. In addition, comparable T(m) studies using oligodeoxyribonucleotides incorporating acyl (RC(O)-) groups and alkoxyacyl (RO(CH(2))(n)C(O)-) groups having the same chain length show that the latter tend to exhibit higher T(m) values than the former. It turned out that 4-N-alkoxycarbonyldeoxycytidines can form base pairs not only with deoxyguanosine but also with deoxyadenosine. Based on the ab initio calculations of the hydrogen bond energies of the possible base pairs formed between 4-N-methoxycarbonyl-1-methylcytosine and 9-methyladenine and the NMR analysis of the base-pairs of (15)N-labeled 4-N-alkoxycarbonyldeoxycytidines with deoxyadenosine derivatives, we conclude that the base pair involves two unique hydrogen bonds between the cytosyl 4-NH group and the adenyl N(1) atom and between the O atom of the ester group and the adenyl 6-NH group.
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, Nagatsuta, Midoriku, Yokohama 226-8501, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kobori
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miyata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ushioda
authors.forename: Kohji
authors.initials: K
authors.lastname: Seio
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sekine
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D003841:Deoxycytidine / Q000737:chemistry*; D007422:Intestines / Q000201:enzymology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012313:RNA / Q000737:chemistry; D012910:Snake Venoms / Q000201:enzymology; D013936:Thymidine / Q000737:chemistry; D014529:Uridine / Q000737:chemistry
chemical_list: D009838:Oligodeoxyribonucleotides; D012910:Snake Venoms; D003841:Deoxycytidine; D012313:RNA; D004247:DNA; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom; D000241:Adenosine; D013936:Thymidine; D014529:Uridine