Synthesis and Characterization of Cell-Permeable Oligonucleotides Bearing Reduction-Activated Protecting Groups on the Internucleotide Linkages.
Cell-permeable oligodeoxyribonucleotides (ODNs) bearing reduction-activated protecting groups were synthesized as oligonucleotide pro-drugs. Although these oligonucleotides were amenable to solid-phase DNA synthesis and purification, the protecting group on their phosphodiester moiety could be readily cleaved by nitroreductase and NADH. Moreover, these compounds exhibited good nuclease resistance against 3'-exonuclease and endonuclease and good stability in human serum. Fluorescein-labeled ODNs modified with reduction-activated protecting groups showed better cellular uptake compared with that of naked ODNs.
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University , 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan.
Hisao
H
Saneyoshi
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University , 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan.
Koichi
K
Iketani
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University , 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan.
Kazuhiko
K
Kondo
Brain Science Institute RIKEN , 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan.
Takeo
T
Saneyoshi
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University , 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan.
Itaru
I
Okamoto
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University , 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan.
Akira
A
Ono
D001483:Base Sequence; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D006801:Humans; D009243:NAD / Q000378:metabolism; D009601:Nitroreductases / Q000378:metabolism; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability
D009841:Oligonucleotides; D009243:NAD; D009601:Nitroreductases