Unanticipated differences between alpha- and gamma-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates.
Unanticipated differences between alpha- and gamma-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates.
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DOI：
10.1093/nar/gkl1025
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发表时间：
2007
影响因子：
14.9
通讯作者：
Dervan PB
中科院分区：
文献类型：
--
作者：
Tsai SM;Farkas ME;Chou CJ;Gottesfeld JM;Dervan PB
将含有α-二氨基丁酸（α-DABA）旋段的发夹聚酰胺-氯苯偶联物与其含有表征良好的γ-DABA旋段的构象异构体进行了比较。虽然未偶联的聚酰胺的dna结合特性相似，但α-DABA偶联物的烷基化特异性增加，反应速率降低。α-DABA与γ-DABA发夹偶联物对人结肠癌细胞系的毒性差异很小，但对细胞形态和G2/M期细胞周期阻滞的影响相似。然而，观察到两类药物在动物毒性方面的显著差异。虽然用α-DABA发夹聚酰胺处理的小鼠与对照小鼠没有显著差异，但类似的γ-DABA发夹是致命的。这种微妙的结构变化带来的巨大差异是无法预测的。
Hairpin polyamide–chlorambucil conjugates containing an α-diaminobutyric acid (α-DABA) turn moiety are compared to their constitutional isomers containing the well-characterized γ-DABA turn. Although the DNA-binding properties of unconjugated polyamides are similar, the α-DABA conjugates display increased alkylation specificity and decreased rate of reaction. Treatment of a human colon carcinoma cell line with α-DABA versus γ-DABA hairpin conjugates shows only slight differences in toxicities while producing similar effects on cell morphology and G2/M stage cell cycle arrest. However, striking differences in animal toxicity between the two classes are observed. Although mice treated with an α-DABA hairpin polyamide do not differ significantly from control mice, the analogous γ-DABA hairpin is lethal. This dramatic difference from a subtle structural change would not have been predicted.
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影响因子：
5.8
作者：
SUNTERS, A;SPRINGER, CJ;HARTLEY, JA
通讯作者：
HARTLEY, JA
影响因子：
15
作者：
Herman, DM;Baird, EE;Dervan, PB
通讯作者：
Dervan, PB
DOI：
10.1073/pnas.2035074100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Best, TP;Edelson, BS;Dervan, PB
通讯作者：
Dervan, PB
影响因子：
4.3
作者：
Alvarez, David;Chou, C. James;Gottesfeld, Joel M.
通讯作者：
Gottesfeld, Joel M.
影响因子：
15
作者：
Swalley, SE;Baird, EE;Dervan, PB
通讯作者：
Dervan, PB