Bailly Christian, Chessari Gianni, Carrasco Carolina, Joubert Alexandra, Mann John, Wilson W David, Neidle Stephen
INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France.
Nucleic Acids Res. 2003 Mar 1;31(5):1514-24. doi: 10.1093/nar/gkg237.
The binding of two symmetric bis-benzimidazole compounds, 2,2-bis-[4'-(3"-dimethylamino-1"-propyloxy)phenyl]-5,5-bi-1H-benzimidazole and its piperidinpropylphenyl analog, to the minor groove of DNA, have been studied by DNA footprinting, surface plasmon resonance (SPR) methods and molecular dynamics simulations in explicit solvent. The footprinting and SPR methods find that the former compound has enhanced affinity and selectivity for AT sequences in DNA. The molecular modeling studies have suggested that, due to the presence of the oxygen atom in each side chain of the former compound, a water molecule is immobilized and effectively bridges between side chain and DNA base edges via hydrogen bonding interactions. This additional contribution to ligand-DNA interactions would be expected to result in enhanced DNA affinity, as is observed.
通过DNA足迹法、表面等离子体共振(SPR)方法以及在显式溶剂中的分子动力学模拟,研究了两种对称的双苯并咪唑化合物,即2,2-双-[4'-(3"-二甲氨基-1"-丙氧基)苯基]-5,5-联-1H-苯并咪唑及其哌啶丙基苯基类似物与DNA小沟的结合情况。足迹法和SPR方法发现,前一种化合物对DNA中的AT序列具有增强的亲和力和选择性。分子建模研究表明,由于前一种化合物每个侧链中存在氧原子,一个水分子被固定,并通过氢键相互作用有效地在侧链和DNA碱基边缘之间形成桥梁。正如所观察到的,这种对配体-DNA相互作用的额外贡献预计会导致DNA亲和力增强。