Potent activity against K562 cells by polyamide-seco-CBI conjugates targeting histone H4 genes.
Potent activity against K562 cells by polyamide-seco-CBI conjugates targeting histone H4 genes.
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针对组蛋白 H4 基因的聚酰胺-seco-CBI 缀合物对 K562 细胞具有有效活性。
DOI：
10.1016/j.bmc.2009.11.005
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发表时间：
2010
影响因子：
3.5
通讯作者：
H. Sugiyama
中科院分区：
文献类型：
--
作者：
Masafumi Minoshima;James Chou;S. Lefebvre;T. Bando;K. Shinohara;J. Gottesfeld;H. Sugiyama
我们设计并合成了吡咯-咪唑聚酰胺和开环-CBI之间的缀合物，其在组蛋白H4基因的编码区内烷基化。研究了DNA对组蛋白H4片段的烷基化活性和对K562慢性粒细胞白血病细胞的作用。其中一种偶联物5-CBI对组蛋白H4基因片段显示出较强的DNA烷基化活性和较好的序列特异性。5-CBI处理后K562细胞组蛋白H4基因表达下调，并能有效诱导细胞凋亡。全局基因表达数据显示，许多组蛋白H4基因被5-CBI处理下调。这些结果表明，序列特异性DNA烷化剂可能具有针对特定基因的癌症化疗的潜力。
We designed and synthesized conjugates between pyrrole–imidazole polyamides and seco-CBI that alkylate within the coding regions of the histone H4 genes. DNA alkylating activity on the histone H4 fragment and cellular effects against K562 chronic myelogenous leukemia cells were investigated. One of the conjugates, 5-CBI, showed strong DNA alkylation activity and good sequence specificity on a histone H4 gene fragment. K562 cells treated with 5-CBI down-regulated the histone H4 gene and induced apoptosis efficiently. Global gene expression data revealed that a number of histone H4 genes were down-regulated by 5-CBI treatment. These results suggest that sequence-specific DNA alkylating agents may have the potential of targeting specific genes for cancer chemotherapy.
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影响因子：
3.5
作者：
Belitsky, JM;Nguyen, DH;Dervan, PB
通讯作者：
Dervan, PB
影响因子：
2.9
作者：
HURLEY, LH;LEE, CS;ARISTOFF, PA
通讯作者：
ARISTOFF, PA
影响因子：
158.5
作者：
Druker, BJ;Talpaz, M;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
158.5
作者：
Druker, BJ;Sawyers, CL;Talpaz, M
通讯作者：
Talpaz, M
Distamycin A 通过 duocarmycin A 调节 DNA 烷基化的序列特异性。
DOI：
10.1073/pnas.93.25.14405
发表时间：
1996
影响因子：
11.1
作者：
Sugiyama,H;Lian,C;Isomura,M;Saito,I;Wang,AH
通讯作者：
Wang,AH