title: Improved strategies for postoligomerization synthesis of oligodeoxynucleotides bearing structurally defined adducts at the N2 position of deoxyguanosine.
abstract: Improved methodology has been developed for preparation of oligodeoxynucleotides bearing adducts on the N2 position of guanine in which the adduction reaction is carried out in homogeneous solution rather than while the oligonucleotide is immobilized on a solid matrix. The methodology utilizes a new synthon, 2-fluoro-O6-(trimethylsilylethyl)-2'-deoxyinosine (3). Nucleoside 3 is stable to the conditions of oligonucleotide synthesis, but the O6 protection is eliminated under very mild conditions following displacement of the 2-fluoro group by amine nucleophiles. Oligonucleotides containing 3 could be removed from the solid support by treatment with 0.1 M NaOH (8 h, rt) without disruption of 3. Reaction of the crude, partially deprotected oligonucleotide with (R)-2-amino-2-phenylethanol in homogeneous solution, followed by removal of the remaining protective groups with NH4OH (60 degrees C, 8 h) and then 0.1% acetic acid, gave the adducted oligonucleotide in good purity and yield. Alternatively, fully deprotected oligonucleotide containing 3 could be prepared by use of labile phenoxyacetyl-type protecting groups on the exocyclic amino groups.
authors.affiliation: Chemistry Department, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: DeCorte
authors.forename: D
authors.initials: D
authors.lastname: Tsarouhtsis
authors.forename: S
authors.initials: S
authors.lastname: Kuchimanchi
authors.forename: M D
authors.initials: MD
authors.lastname: Cooper
authors.forename: P
authors.initials: P
authors.lastname: Horton
authors.forename: C M
authors.initials: CM
authors.lastname: Harris
authors.forename: T M
authors.initials: TM
authors.lastname: Harris
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D004852:Epoxy Compounds / Q000737:chemistry; D007288:Inosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D007700:Kinetics; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000138:chemical synthesis*; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis*
chemical_list: D018736:DNA Adducts; D004852:Epoxy Compounds; D009841:Oligonucleotides; D014297:Trimethylsilyl Compounds; C101064:2-fluoro-(O(6)-trimethylsilylelthyl)-2'-deoxyinosine; D007288:Inosine; C013690:styrene oxide; D003849:Deoxyguanosine