title: Polymerase-mediated high-density incorporation of amphiphilic functionalities into DNA: enhancement of nuclease resistance and stability in human serum.
abstract: Modified oligodeoxyribonucleotides (mdODNs) bearing multiple copies of an amphiphilic functional group were enzymatically synthesized by simultaneous incorporation of base-modified 5'-triphosphate analogs of 2'-deoxyguanosine (dG(am)TP), 2'-deoxyuridine (dU(am)TP), 2'-deoxyadenosine (dA(am)TP), and 2'-deoxycytosine (dC(am)TP). The amphiphilic functionality, that is, (E)-38,53-dioxo-2,5,8,11,14,17,20,23,26,29,32,35-dodecaoxa-39,52-diazapentapentacont-54-en-55-yl group, consists of the water soluble dodeca(ethylene glycol) chain and the hydrophobic dodecyl chain. An enzymatically synthesized ODN, composed of a 20-mer 5'-terminal segment containing 2'-O,4'-C-methylene-bridged/linked bicyclic ribonucleotide (B/L nucleotide) and a 12-mer 3'-terminal segment containing the nucleobase-modified analogs, exhibits very high resistance against phosphodiesterase I and is stable in human serum for a longer period when compared with ODN, where the 12-mer 3'-terminal segment contains unmodified nucleotides.
authors.affiliation: Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan; National Institute of Biomedical Innovation (NIBIO), 7-6-8 Asagi, Saito, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yuuya
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozaki
authors.affiliation: Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan. Electronic address: mkuwa@gunma-u.ac.jp.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kuwahara
mesh_terms: D004247:DNA / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D043264:Phosphodiesterase I / Q000378:metabolism*; D044967:Serum / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D043264:Phosphodiesterase I
keywords: Amphiphilic functionality; Biostability; DNA polymerase; High-density incorporation; Modified nucleoside triphosphate