含烷基链环多胺衍生物的合成及其与DNA作用研究

以1,4,7,10-四氮杂环十二烷(cyclen)为原料,合成了一系列具有不同长度烷基侧链的四氮十二杂环类化合物,并用氢谱、碳谱、高分辨质谱进行了结构表征.用DNA热变性分析和琼脂糖凝胶电泳实验分别研究了此系列化合物与小牛胸腺DNA(CT DNA)的结合能力和对超螺旋DNA(pBR322 DNA)的断裂作用.结果表明,在pH7.2 Tris-HCl缓冲液中,1,4,7,10-四(正辛基)-1,4,7,10-四氮杂环十二烷(h)与CT DNA的结合能力最强,CT DNA的熔点上升幅度最大(ΔTm=5.22℃),且存在明显的插入结合作用,但切割DNA的能力很弱.由此可见,亲脂性烷基侧链长度的增长有利于增加化合物与DNA的相互结合,但不能提高化合物切割DNA的活性.

Synthesis and DNA Binding Properties of the Cyclen Derivatives Containing Alkyl Carbon Chains

Cyclen derivatives containing lipophilic alkyl carbon chains with different length were synthesized from 1,4,7,10-tetraazacyclododecane(cyclen),and fully characterized by 1H NMR,13C NMR,HRMS.The interactions of DNA and N-alkylated cyclen derivatives were carried out.Their binding abilities of CT DNA and cleavage of pBR322 DNA were investigated by DNA thermal denaturation and gel electrophoresis,respectively.The results suggested that 1,4,7,10-tetraoctyl-1,4,7,10-tetraazacyclododecane(h) enhanced the melting temperature ΔTm of CT DNA by 5.22 ℃ in tris-HCl buffer(pH=7.2),which indicated that this compound(h) exhibited the strongest binding affinity to CT DNA among all tested cyclen derivatives,and this compound(h)was bonded to CT DNA throungh an intercalative mode.However,this compound(h) was not found to cleavage DNA.It is concluded that the increasing lipophilicity enhances their binding to DNA,but don’t improve their cleavage abilities.