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研究了AT-1840类似物与寡聚核苷酸的相互作用与其药理活性之间的关系。根据前期研究的结果选择了具B-DNA结构的四聚核苷酸d(CCGG)_2作为药物作用的靶标。由于核酸双螺旋结构的特点,药物与核酸可以以2种结合方式相互作用,计算结果表明对于具有生物活性的化合物,作用方式A与核苷酸相互作用显著强于作用方式B,而且相互作用与药理活性成平行关系。 根据核苷酸与化合物相互作用的立体效应和电性特征,设计了2个新的化合物。经计算,它们与核酸的相互作用能都强于现有的化合物。
The relationship between AT-1840 analogues and oligonucleotides and their pharmacological activities was investigated. According to the results of the previous study, we selected the tetranucleotide d (CCGG) 2 with B-DNA structure as the target of drug action. Due to the characteristics of the double helix structure of the nucleic acid, the drug and the nucleic acid can interact with each other in two binding modes. The calculation results show that the interaction between the mode A and the nucleotide is stronger than that of the mode B for the biologically active compound, and the interaction Pharmacological activity into a parallel relationship. According to the three-dimensional effect of the interaction between the nucleotide and the compound and the electrical characteristics, two new compounds were designed. Their calculated interactions with nucleic acids are stronger than existing compounds.