合成受体与模型磷酸化肽的相互作用机理

为了研究基于Zn2+-二甲基吡啶胺及胍羰基吡咯基团的配位型受体Zn Dpa G与磷酸化肽的相互作用机制,选取具有不同序列的磷酸化肽作用模型,采用等温滴定微量热法考察了Zn Dpa G与磷酸化肽的结合常数,研究了模型肽中磷酸基团的数量、密度及位置等因素对多肽与受体间结合强度的影响.结果表明,Zn Dpa G受体对双磷酸化肽结合能力显著高于单磷酸化肽,其结合常数可提高10~40倍,2个磷酸基团的距离越近,结合作用越强;而磷酸基团的位置显著影响受体与单磷酸化肽的结合强度.本研究结果为进一步优化磷酸化肽受体结构设计,实现肽与受体间高选择性识别提供了一定的理论依据.

Interaction Mechanism Between Synthetic Receptor and Model Phosphorylated Peptides

Study on interaction mechanism between synthetic receptor and phosphorylated peptides is of great importance for phophopeptide enrichment and early disease-detection. In this study, association between Zn2+-coordination type synthetic receptor and some model phosphorylated peptides was studied, the receptor contains Zn2+-dipicolylamine and guanidiniocarbonyl pyrrole tethered by hydrophobic spacer. Isothermal titration calorimetry was used to elucidate the association thermodynamics. The receptor displayed higher affinity to bis-phosphorylated peptides in comparison with mono-phosphorylated peptides, and the association constant was 10—40 times higher for bis-phosphorylated peptides than that of mono-phosphorylated peptides. Space between the two phosphate groups showed great influence on the association, i.e. association constant remar-kably decreased as the space increased. For mono-phosphorylated peptides, the position of phosphate in the sequence affected the affinity. The results are expected to provide insights into the principle for the design of receptor for peptides.