利用超分子体系模拟生物体G蛋白耦联受体型信号转导过程

Investigation of Bio-inspired Signal Transduction in the Supermolecular System

以生物体G蛋白耦联受体型信号转导过程为模拟原型,利用自组装方法构建了具有分子间信号转导能力的超分子体系。带正电荷的肽脂质分子与人工受体共同形成脂质体,乳酸脱氢酶(LDH)(效应器)通过静电作用吸附到脂质体上,乳酸脱氢酶的竞争性抑制剂(Cu2+)抑制LDH活性(相对酶活性为11.6%),进而共同组成了一个酶活性处于关闭状态的超分子系统。向超分子体系中加入信号分子——磷酸吡哆醛(PLP)后,PLP通过静电作用吸附到带正电荷的脂质体表面,并与人工受体形成希夫碱;希夫碱与LDH竞争铜离子,解除铜离子对LDH活性的抑制,恢复LDH的催化活性,使相对酶活性达到83.0%。实验结果表明,超分子体系完成了从信号分子到效应器(酶)活性变化的信号转导过程,可以利用超分子体系构建调控酶催化活性的超分子器件。

A supermolecular system with intermolelular communication activities was constructed,inspired by G-protein mediated cell signal transduction.A cationic peptide lipid,N,N-dihexadecyl-Nα-[6-（trimethylammonio）hexanoyl]-alaninamide bromide（N＋C5Ala2C16）and an artificial receptor were synthesized with 1-hexadecylamine and 1-bromohexadecane as starting material through five steps,including substitution and condensation reactions.A self-assembled supermolecular system was obtained,based on liposome with positive charges.The relative activity of LDH was 11.6 % due to the inhibition of Cu2＋ in the absence of the signal molecules.In that supermolecular system,pyridoxal 5′-phosphate acted as the artificial signal,Cu2＋ acted as a mediator.When the signal molecule,PLP,was added to the supermolecular system,PLP attached to liposome surface,and reacted with the amino group of the artificial receptor,and formed the Schiff base.The Schiff base could withdraw the copper cation captured by LDH,and led to the recovery of LDH activity,up to 83.0 %,which has been inhibited by copper cation ever.The given results showed that the supermolecular system finished the signal transduction from the signal molecules to the effect enzyme.A series of nanodevice,such as the supermolecular switch,will be created to control the enzyme activities.