长春新碱与人血清白蛋白的相互作用研究  

Investigation on the Interaction of Vincristine with Human Serum Albumin

作　　者：陈克海[1] 郑学仿[1] 郭明[2] 曹洪玉[1] 唐乾[1] 杨彦杰[1] 

机构地区：[1]大连大学辽宁省生物有机化学重点实验室,大连116622 [2]大连大学环境与化学工程学院,大连116622

出　　处：《化学学报》2007年第17期1887-1891,共5页Acta Chimica Sinica

基　　金：国家自然科学基金(No.20271010);辽宁省优秀人才培养计划项目(No.RC-04-10)资助项目.

摘　　要：利用荧光和圆二色光谱研究了长春新碱(VCR)与人血清白蛋白(HSA)之间的相互作用.通过荧光猝灭测得在288,298和308K时,VCR与HSA的结合常数K分别为2.14×104,1.73×104和1.35×104L·mol-1,表明VCR与HSA间具有较强的结合作用,属于静态猝灭.计算出焓变(△H)为-17.38kJ·mol-1,熵变(△S)为22.62J·mol-1·K-1,结合分子模型理论计算的结果,表明VCR与HSA相互作用时在色氨酸(Trp)214残基和VCR分子中吲哚基间作用力以疏水作用力为主,但在VCR和HSA分子间以静电引力为主.圆二色光谱(CD)的数据表明相互作用后HSA的二级结构发生了改变:HSA的α-螺旋的含量从51.7%下降到32.9%,β-折叠的含量增加了9.2%.The interaction between vincristine （VCR） and human serum albumin （HSA） was investigated by fluorescence and circular dichroism （CD） spectra at 288, 298 and 308 K. With fluorescence quenching method, the binding constants K were determined to be 2.14× 10^4, 1.73× 10^4 and 1.35× 10^4 L·moL^-1 respectively, indicating that the binding of VCR to HSA was strong, and the quenching mechanism was a static quenching. Enthalpy change （AH） was calculated to be - 17.38 kJ·moL^-1 and entropy change （AS） was 22.62 J·mol^-1·K^-1. Taking into account the result of molecule modeling study, all these results indicated that the hydrophobic interaction played major roles between the tryptophan （214） residue of HSA and the indole moiety of VCR, but the electrostatic interaction mostly existed between the molecules of HSA and VCR in the binding process. The secondary structure of HSA was altered （CD data） with reductions of a-helices from 51.7% to 32.9%, but increases β-sheet by about 9.2% after VCR bound to HSA.

关 键 词：长春新碱 人血清白蛋白 荧光光谱 圆二色光谱 

分 类 号：R96[医药卫生—药理学]