A new class of polyintercalating molecules

被引:104
作者
Lokey, RS
Kwok, Y
Guelev, V
Pursell, CJ
Hurley, LH
Iverson, BL
机构
[1] UNIV TEXAS,DEPT CHEM,AUSTIN,TX 78712
[2] UNIV TEXAS,DEPT BIOCHEM,AUSTIN,TX 78712
[3] UNIV TEXAS,DEPT PHARM,AUSTIN,TX 78712
[4] TRINITY UNIV,DEPT CHEM,SAN ANTONIO,TX 78212
关键词
D O I
10.1021/ja9706108
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We have synthesized a series of polyintercalating compounds, including the first known tetraintercalator, based on the 1,4,5,8-naphthalenetetracarboxylic diimide chromophore. The chromophores are attached in a head-to-tail arrangement by peptide linkers and are synthesized by standard solid phase peptide synthesis methods. We report evidence, based on UV-visible spectroscopy and viscometry, that the compounds are fully intercalated upon binding to double-stranded DNA. Using DNAse I footprinting experiments, the bisintercalator 2 was found to bind to DNA in a cooperative manner. The footprinting results as well as association and dissociation kinetics data reveal that the compounds exhibit a tremendous preference for GC over AT sequences. A. mode of binding is proposed in which the compounds intercalate completely from the major groove, and not in a threading manner as may be suggested by their structures. A kinetic scheme is proposed that takes into account the observed cooperativity and fits the data for the dissociations of the polyintercalators from poly(dAdT), although a similar scheme could not adequately model their dissociations from poly(dGdC) or from calf thymus DNA.
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页码:7202 / 7210
页数:9
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