MOLECULAR RECOGNITION BETWEEN LIGANDS AND NUCLEIC-ACIDS - NOVEL PYRIDINE-CONTAINING AND BENZOXAZOLE-CONTAINING AGENTS RELATED TO HOECHST-33258 THAT EXHIBIT ALTERED DNA-SEQUENCE SPECIFICITY DEDUCED FROM FOOTPRINTING ANALYSIS AND SPECTROSCOPIC STUDIES
MOLECULAR RECOGNITION BETWEEN LIGANDS AND NUCLEIC-ACIDS - NOVEL PYRIDINE-CONTAINING AND BENZOXAZOLE-CONTAINING AGENTS RELATED TO HOECHST-33258 THAT EXHIBIT ALTERED DNA-SEQUENCE SPECIFICITY DEDUCED FROM FOOTPRINTING ANALYSIS AND SPECTROSCOPIC STUDIES
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DOI：
10.1021/tx00015a013
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发表时间：
1990-05-01
影响因子：
4.1
通讯作者：
LOWN, JW
中科院分区：
文献类型：
--
作者：
BATHINI, Y;RAO, KE;LOWN, JW
描述了DNA小沟结合剂Hoechst 33258的某些类似物的合成，所述类似物被设计为表现出改变的序列识别。结构修饰包括以下内容：吡啶取代苯并咪唑部分的苯环，在相对于DNA受体的两个可能方向上用苯并恶唑取代一个苯并咪唑单元，以及合成2，2“-间亚苯基双[6-（4-甲基-1-哌嗪基）苯并咪唑]。通过MPE足迹法测定这些试剂对pBR 322 DNA的HindIII/EcoRI片段的序列识别。与Hoechst 33258相比，一些类似物表现出改变的DNA序列偏好。特别地，带有苯并恶唑部分的结构，其中氧与向内定向的吡啶氮一起向内定向到小沟，似乎赋予结合序列内的GC碱基对的识别性质。可能的因素结构，立体化学和静电，有助于改变DNA序列识别性能进行了讨论。
The syntheses of certain analogues of the DNA minor groove binding agent Hoechst 33258 designed to exhibit altered sequence recognition are described. The structural modifications include the following:substitution of pyridine for the benzene ring of the benzimidazole moiety, replacement of one benzimidazole unit by a benzoxazole in the two possible orientations with respect to the DNA receptor, and a synthesis of 2,2''-m-phenylenebis[6-(4-methyl-1-piperazinyl)benzimidazole]. Sequence recognition of these agents on a HindIII/EcoRI fragment of pBR322 DNA was determined by MPE footprinting procedures. Some of the analogues exhibited altered DNA sequence preference compared with Hoechst 33258. In particular, a structure bearing a benzoxazole moiety with the oxygen oriented inward to the minor groove together with an inward-directed pyridine nitrogen appears to confer the property of recognition of a GC base pair within the binding sequence. The possible factors structural, stereochemical, and electrostatic, contributing to the altered DNA sequence recognition properties are discussed.