Cellular Uptake of Oligodeoxyribonucleoside Methylphosphonates
作者:
JOEL T. LEVIS,
WILLIAM O. BUTLER,
BEN Y. TSENG,
PAUL O.P. TS'O,
期刊:
Antisense Research and Development
(MAL Available online 1995)
卷期:
Volume 5,
issue 4
页码: 251-259
ISSN:1050-5261
年代: 1995
DOI:10.1089/ard.1995.5.251
数据来源: MAL
摘要:
The cellular uptake of oligodeoxyribonucleoside methylphosphonates has been evaluated using three radiolabeled oligomers. Oligomers I and II ([3H]-T8and [3H]-T16, respectively) are nonionic methylphosphonate oligomers labeled with tritium on the phosphonate internucleotide linkage. EDA-III contains a single phosphodiester linkage, a [32P]-label and an ethylenediamine conjugate at the [32P]-5′-end. All three oligomers are stable in cells. At a 1 μM concentration, oligomer I is not taken up by human erythrocytes. The octanol/DPBS partition coefficients for oligomers I and II (1.5 x 10-4and 4.2 x 10-4, respectively) further indicate that these molecules should not diffuse across cell membranes at appreciable rates. Oligomer I is taken up by HL-60 cells, although at a slower rate than the uptake of the fluid-phase marker sucrose. The cell-associated levels of oligomer II in K-562 cells following incubation of cells with the oligomer for 2 days is independent of concentration and nonsaturable, suggesting a mechanism of uptake independent of receptor. Finally, the initial uptake rate of EDA-III in mouse L cells is greater than the uptake of two oligodeoxyribonucleotides (T8,T16), reaching a plateau after 3 hours incubation with cells. These observations should aid in the elucidation of the mechanism by which this class of antisense agents enters the intracellular environme
点击下载:
PDF
(6876KB)
返 回