Teasdale R M, Matson S J, Fisher E, Krieg A M
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Antisense Res Dev. 1994 Winter;4(4):295-7. doi: 10.1089/ard.1994.4.295.
Whole and partially modified phosphorothioate oligodeoxynucleotides (ODN) were found to directly inhibit T4 polynucleotide kinase (PNK) activity, while phosphodiester ODN showed no detectable inhibition. This inhibition was found to be length dependent, as demonstrated by a 28-mer phosphorothioate ODN with an IC50 of 12 nM, and an 8-mer phosphorothioate ODN with an IC50 of 27,000 nM. Inhibition depended on the number and type of modified internucleotide linkages: a 20-mer phosphorothioate ODN had an IC50 of 21 nM, while a chimeric ODN with seven phosphorothioate linkages and an identical sequence showed no inhibition. On the other hand, the same sequence as a chimeric phosphorodithioate ODN (with seven dithioate linkages) had an IC50 of 580 nM. Four different chimeric phosphorodithioate ODN showed markedly different potencies of inhibition, suggesting that inhibition of PNK activity can be sequence specific.
发现全硫代磷酸酯寡脱氧核苷酸（ODN）和部分修饰的硫代磷酸酯寡脱氧核苷酸可直接抑制T4多核苷酸激酶（PNK）的活性，而磷酸二酯寡脱氧核苷酸则未表现出可检测到的抑制作用。这种抑制作用被发现与长度有关，如一个IC50为12 nM的28聚体硫代磷酸酯寡脱氧核苷酸和一个IC50为27000 nM的8聚体硫代磷酸酯寡脱氧核苷酸所证明。抑制作用取决于修饰的核苷酸间连接的数量和类型：一个20聚体硫代磷酸酯寡脱氧核苷酸的IC50为21 nM，而一个具有七个硫代磷酸酯连接且序列相同的嵌合寡脱氧核苷酸则未表现出抑制作用。另一方面，与嵌合二硫代磷酸酯寡脱氧核苷酸（具有七个二硫代磷酸酯连接）相同序列的IC50为580 nM。四种不同的嵌合二硫代磷酸酯寡脱氧核苷酸表现出明显不同的抑制效力，表明对PNK活性的抑制可能具有序列特异性。
