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金属配位在多肽与蛋白质研究中的应用

马晓川, 费浩

化学进展 ›› 2016, Vol. 28 ›› Issue (2/3) :184-192

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化学进展 ›› 2016, Vol. 28 ›› Issue (2/3) :184-192 DOI: 10.7536/PC150625
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金属配位在多肽与蛋白质研究中的应用

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The Use of Metal Coordination in Peptide and Protein Research

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摘要

金属元素常见于天然蛋白质分子中,并扮演着不可或缺的重要角色。对金属与氨基酸的配位方式的不断深入理解,有助于人工设计新型的金属-多肽配位模式,并在多肽结构功能优化、分子组装、标记与成像以及药物设计等领域获得更广泛的研究和应用。本文首先简要介绍蛋白质中的不同基团与金属离子之间的配位模式以及具体的研究案例,进而介绍了金属配位在多肽分子的二级结构调控、超分子结构组装、多肽及蛋白质的荧(磷)光标记、蛋白质折叠方式分析等基础研究中的应用。最后,对上述研究领域为金属-多肽类分子探针或药物的设计优化所提供的发展潜力进行展望。

Abstract

Metal ions are commonly seen in naturally occurring protein molecules, and often play pivotal roles in protein function. Deepening understanding of basic coordination models between amino acids and various metals facilitates artificial designs of novel peptide-metal coordination modalities that can be broadly applied in research fields such as peptide structure-function optimization, molecular assembly, labeling and imaging, and peptide therapeutics development. This minireview introduces the basic coordination chemistry between electron-donating groups on peptides (namely carboxylate, amine, imidazole, sulfhydryl groups) and their respective favorable metal ions with illustrated examples. We next discuss in detail the use of metal or metalloid coordination in fundamental research of peptides and proteins, including secondary structure constraining, supermolecular assembly, fluorescence or phosphorescence labeling, and protein folding analysis. In particular, we highlight two examples of luminogenic peptide/protein labeling techniques, the first being the broadly applied biarsenical ligand and tetracysteine motif based protein probing method, and the second being the recently reported iridium(Ⅲ) complex and histidine motif based peptide labeling technique. Finally we discuss the principles in the development of metallo-peptide molecular probes and the potential brought by this research for optimization in drug designs.

Contents
1 Introduction
2 Common binding groups in peptides for metal coordination
2.1 Carboxyl group
2.2 Amine group and imidazole group
2.3 Sulfhydryl group
3 The effects of metal coordination on peptide/protein structure
3.1 Folding and stabilization
3.2 Supermolecular assembly
4 Coordination-based peptide luminescent labeling and biological applications
5 Outlook

Graphical abstract

关键词

配位化学 / 多肽 / 荧光 / 结构约束

Key words

coordination chemistry / peptide / fluorescence / structure constraining

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马晓川, 费浩. 金属配位在多肽与蛋白质研究中的应用[J]. 化学进展, 2016, 28(2/3): 184-192 DOI:10.7536/PC150625
Ma Xiaochuan, Fei Hao. The Use of Metal Coordination in Peptide and Protein Research[J]. Progress in Chemistry, 2016, 28(2/3): 184-192 DOI:10.7536/PC150625

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