合成受体与模型磷酸化肽的相互作用机理

doi:10.7503/cjcu20140436

高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (1): 171.doi: 10.7503/cjcu20140436

合成受体与模型磷酸化肽的相互作用机理

张赛晖, 师彦涛, 韩亮, 李传光, 王蔚, 袁直()

南开大学高分子化学研究所, 功能高分子材料教育部重点实验室, 天津化学化工协同创新中心, 天津 300071

收稿日期:2014-05-08 修回日期:2014-12-16 出版日期:2015-01-10 发布日期:2014-12-16
作者简介:联系人简介: 袁直, 女, 博士, 教授, 博士生导师, 主要从事生物医用材料研究. E-mail: zhiy@nankai.edu.cn
基金资助:
基金项目: 国家自然科学基金(批准号: 21104034, 51273094)和教育部长江学者创新团队发展计划(批准号: IRT1257)资助

Interaction Mechanism Between Synthetic Receptor and Model Phosphorylated Peptides^†

ZHANG Saihui, SHI Yantao, HAN Liang, LI Chuanguang, WANG Wei, YUAN Zhi^*()

Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300071, China

Received:2014-05-08 Revised:2014-12-16 Online:2015-01-10 Published:2014-12-16
Contact: YUAN Zhi E-mail:zhiy@nankai.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21104034, 51273094) and the Program for Changjiang Scholars and Innovative Research Team of Ministry of Education, China(NoIRT1257)

摘要/Abstract

摘要：

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ZnDpaG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ZnDpaG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, ZnDpaG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.

关键词: 合成受体, 磷酸化肽, 等温滴定微量热

Abstract:

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.

Key words: Synthetic receptor, Phosphorylated peptides, Isothermal titration calorimetry

中图分类号:

O642

TrendMD:

张赛晖, 师彦涛, 韩亮, 李传光, 王蔚, 袁直. 合成受体与模型磷酸化肽的相互作用机理. 高等学校化学学报, 2015, 36(1): 171.

ZHANG Saihui, SHI Yantao, HAN Liang, LI Chuanguang, WANG Wei, YUAN Zhi. Interaction Mechanism Between Synthetic Receptor and Model Phosphorylated Peptides^†. Chem. J. Chinese Universities, 2015, 36(1): 171.

图/表 5

参考文献 23

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Peptide sequence^*	10^-4K/ (L·mol^-1)	10^-4ΔH/ (J·mol^-1)	ΔS/ (J·mol^-1·K^-1)
GGpSpSGGG	8.7±1.2	7.9±1.5	337.2±46.9
GGpSGpSGG	3.6±0.6	13.0±1.3	527.2±62.8
GGpSGGpSG	2.6±0.4	35.1±4.6	202.9±18.4

Peptide sequence^*	10^-4K/ (L·mol^-1)	10^-4ΔH/ (J·mol^-1)	ΔS/ (J·mol^-1·K^-1)
GGpSpSGGG	8.7±1.2	7.9±1.5	337.2±46.9
GGpSGpSGG	3.6±0.6	13.0±1.3	527.2±62.8
GGpSGGpSG	2.6±0.4	35.1±4.6	202.9±18.4

Peptide sequence	10^-3K/ (L·mol^-1)	10^-3ΔH/ (J·mol^-1)	ΔS/ (J·mol^-1·K^-1)
GGGGGpSG	2.4±0.3	3.5±2.1	76.1±5.8
GGGGpSGG	9.8±0.5	4.4±2.3	87.0±5.0
GGGpSGGG	4.6±0.5	0.9±0.1	73.2±1.3
GGpSGGGG	1.7±0.3	4.7±0.9	77.4±3.3

Peptide sequence	10^-3K/ (L·mol^-1)	10^-3ΔH/ (J·mol^-1)	ΔS/ (J·mol^-1·K^-1)
GGGGGpSG	2.4±0.3	3.5±2.1	76.1±5.8
GGGGpSGG	9.8±0.5	4.4±2.3	87.0±5.0
GGGpSGGG	4.6±0.5	0.9±0.1	73.2±1.3
GGpSGGGG	1.7±0.3	4.7±0.9	77.4±3.3

Peptide sequence	10^-3K/ (L·mol^-1)	10^-3ΔH/ (J·mol^-1)	ΔS/ (J·mol^-1·K^-1)
GGGGpSGG	9.8±0.5	4.2±2.1	87.0±5.0
GGGGpSFG	4.5±0.3	9.2±0.4	100.0±5.0
GGGFpSGG	4.7±0.5	10.9±0.4	106.7±8.8

合成受体与模型磷酸化肽的相互作用机理

Interaction Mechanism Between Synthetic Receptor and Model Phosphorylated Peptides^†

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合成受体与模型磷酸化肽的相互作用机理

Interaction Mechanism Between Synthetic Receptor and Model Phosphorylated Peptides†

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Interaction Mechanism Between Synthetic Receptor and Model Phosphorylated Peptides^†