Abstract
Antisense conjugate DNA covalently bound to functional amines, sugars or peptides such as nuclear localization signals (NLS), nuclear export signals (NES) and artificial amphiphilic alpha-helical and beta-sheet peptides were synthesized by solid phase fragment condensation (SPFC). Inhibitory effects on human telomerase of synthesized antisense conjugate DNAs were evaluated by TRAP assay. Antisense conjugate DNAs showed several times higher inhibitory effects on telomerase activity compared to native antisense DNA in cell lysis solutions. Antisense conjugate DNAs showed comparable or higher as same as inhibitory activity compared with antisense phosphorothioate DNA (S-DNA). Interestingly, antisense conjugate DNA showed much higher inhibition against telomerase activity with native antisense DNA or antisense phosphorothioate DNA in cellular system. We observed enhanced cellular uptake and positively controlled intracellular localization of conjugate DNAs by use of confocal fluorescent microscope.
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