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

被引:91
作者
BATHINI, Y [1 ]
RAO, KE [1 ]
SHEA, RG [1 ]
LOWN, JW [1 ]
机构
[1] UNIV ALBERTA,DEPT CHEM,EDMONTON T6G 2G2,ALBERTA,CANADA
关键词
D O I
10.1021/tx00015a013
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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. © 1990, American Chemical Society. All rights reserved.
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页码:268 / 280
页数:13
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