Recognition of the DNA Minor Groove by Thiazotropsin Analogues
Recognition of the DNA Minor Groove by Thiazotropsin Analogues
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DOI：
10.1002/cbic.201402202
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发表时间：
2014-09-05
期刊：
影响因子：
3.2
通讯作者：
Parkinson, John A.
中科院分区：
文献类型：
--
作者：
Alniss, Hasan Y.;Salvia, Marie-Virginie;Parkinson, John A.
溶液相自缔合特性和DNA分子识别特性的报告为三个紧密的类似物的小沟结合配体从thiazotropsin类lexitropsin分子，他们将异丙基噻唑作为亲脂性的建筑块。硫促生长素B（AcIm-Py（iPr）ThDp）显示出与硫促生长素A（FoPyPy（iPr）ThDp）相似的自组装特征，尽管通过掺入咪唑代替N-甲基吡咯将其DNA识别靶标从5 ′-ACTAGT-3 ′交换为5 ′-ACGCGT-3 ′而对其进行了工程改造。在AIK-18/51中通过烟酰胺替换甲酰胺头基导致溶液相自组装特征的可测量差异和显著增强的DNA缔合特征。自组装配体聚集体及其与各自的DNA靶标的复合物的结构和相关的热力学参数被认为是在簇靶向DNA的小沟复合物的背景下。
Solution-phase self-association characteristics and DNA molecular-recognition properties are reported for three close analogues of minor-groove-binding ligands from the thiazotropsin class of lexitropsin molecules; they incorporate isopropyl thiazole as a lipophilic building block. Thiazotropsin B (AcIm-Py(iPr)ThDp) shows similar self-assembly characteristics to thiazotropsin A (FoPyPy(iPr)ThDp), although it is engineered, by incorporation of imidazole in place of N-methyl pyrrole, to swap its DNA recognition target from 5'-ACTAGT-3' to 5'-ACGCGT-3'. Re-placement of the formamide head group in thiazotropsin A by nicotinamide in AIK-18/51 results in a measureable difference in solution-phase self-assembly character and substantially enhanced DNA association characteristics. The structures and associated thermodynamic parameters of self-assembled ligand aggregates and their complexes with their respective DNA targets are considered in the context of cluster targeting of DNA by minor-groove complexes.