受体的分子结构对超分子体系人工信号转导过程的影响

The Influence of Receptor Structure on the Characteristics of Artificial Signal Transduction in Supramolecular System

利用仅存在甲基差异的两种人工受体研究受体的分子结构对超分子体系的人工信号转导过程的影响。分别合成了用于组建人工信号转导系统的阳离子型肽脂质(N+C5Ala2C16)和两种在活性氨基的邻位上存在甲基差异的人工受体:N,N-二-十六烷基-甘氨酰胺(Gly2C16)和N,N-二-十六烷基-丙氨酰胺(Ala2C16)。分别以两种受体构建了表达信号转导机能的超分子体系,利用紫外-可见光谱检测了两种受体与信号分子吡哆醛磷酸(PLP)的作用特点及通过第二信使(Cu2+)启动乳酸脱氢酶(LDH)报告系统的特点。结果表明:甲基使人工受体与信号分子的表观结合常数下降(甘氨酰类脂受体为246000,丙氨酰类脂受体为120000)、使人工受体-信号分子复合物的紫外吸收发生红移、使人工受体-信号分子-第二信使分子复合物的紫外吸收发生红移、并降低信号分子对LDH报告系统的激活活性(甘氨酰类脂受体可恢复到至92.8%,丙氨酰类脂只恢复到83%)。证明了人工受体中的甲基抑制了类脂受体与信号分子的结合,并影响超分子体系的人工信号转导活性。

The functional characteristics of amino acid residues of glycine or alanine in artificial receptor an chored on artificial vesicle membranes of the artificial signal transduction system were detected by means of UV-Vis spectrometry. A cationic peptide lipid named E N,N-dihexadecyl-Na-[6- （trimethylammonio） hex anoyl] -alaninamidebromide] （N＋ C5 Ala2C） and two artificial receptor named aminoacyl-lipids IN, N-di hexadecyl-glyninamide （Gly2C,6） and N, N-dihexadecyl -alaninamide （Ala2C16）] were synthesized. The supramolecular system was individually constructed in HEPES buffer （pH 7.00） at 40. Experimental results showed that the reaction between aminoacyl-lipid and pyridoxal 5＇-phosphate was affected by the side-chain groups of the amino acids in aminoacyl-lipids. The apparent binding constant of artificial receptors and signaling molecules was 246,000 in GIy2C6 receptor system, but was 120,000 in Ala2CI receptor system. Because of the ortho-methyl group, the ultraviolet absorption of the complexes ofartificial receptors and signal molecules showed a red shift, the ultraviolet absorption of artificial receptors - signaling molecules - the second messenger molecules compounds also showed a red shift, and the activity of artificial receptor to recover the activation of signal molecules on LDH report system declined from 92. 8% in Gly2C16 receptor system to 83% in Ala2C16 receptor system. The experimental conclusion was that the ortho-methyl group inhibited the activity of the amino group in Ala2C16receptor to recognize and bind the artificial signal molecule, and reduced the activities of artificial signal transduction in supramolecular system.