分子印迹技术在蛋白质分离分析中的研究进展

doi:10.3724/SP.J.1123.2019.06017

色谱 ›› 2020, Vol. 38 ›› Issue (1): 50-59.DOI: 10.3724/SP.J.1123.2019.06017

分子印迹技术在蛋白质分离分析中的研究进展

孙晓宇¹^,², 马润恬¹, 师彦平¹^,^*()

¹ 中国科学院兰州化学物理研究所, 中国科学院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室, 甘肃兰州 730000
² 中国科学院大学, 北京 100049

收稿日期:2019-06-19 出版日期:2020-01-08 发布日期:2020-12-11
通讯作者: 师彦平
作者简介:师彦平, E-mail:shiyp@licp.cas.cn
基金资助:
国家自然科学基金项目(21575150);国家自然科学基金项目(21775153);国家自然科学基金项目(21804135);中国科学院"西部之光"人才培养引进计划-西部青-学者项目（B类）

Recent advances in molecular imprinting technology for the separation and analysis of proteins

SUN Xiaoyu¹^,², MA Runtian¹, SHI Yanping¹^,^*()

¹ CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
² University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, China

Received:2019-06-19 Online:2020-01-08 Published:2020-12-11
Contact: SHI Yanping
Supported by:
National Natural Science Foundation of China(21575150);National Natural Science Foundation of China(21775153);National Natural Science Foundation of China(21804135);Scholar Program of West Light Project, Chinese Academy of Sciences

摘要/Abstract

摘要：

蛋白质结构复杂，种类多样，与各种生命活动密切相关。大部分蛋白质在生物体中含量极低，对其分析检测带来极大困难。因此实现复杂生物样品中蛋白质的选择性识别与分离，对实现蛋白质的分离分析意义重大。通过分子印迹技术制备的分子印迹聚合物含有与模板分子大小、形状一致，官能团相互匹配的三维印迹空穴，在蛋白质的选择性识别与分离领域显示出了巨大的发展潜力。但是，由于蛋白质具有尺寸较大、构型易变、结构复杂等特点，分子印迹技术在蛋白质印迹中面临着巨大挑战。该文在介绍几种新型分子印迹技术包括表面印迹、抗原决定基印迹和金属螯合物印迹的基础上，综述了近3年分子印迹技术在蛋白质分离分析方面的应用，并对其发展进行了总结与展望。

关键词: 分子印迹, 蛋白质, 分离分析, 综述

Abstract:

Proteins, which have complex structures and fall under diverse categories, are closely associated with different kinds of life activities. Majority of the proteins exist in low concentrations in complex biological samples, because of which their direct analysis without sample pretreatment is difficult. Thus, selective separation of the target proteins from complex biological samples is essential for efficient analysis. Molecularly imprinted polymers, containing numerous imprinted cavities that are complementary with the templates in terms of shape, size, and functional groups, have great potential for use in the selective recognition and separation of the target proteins from complex biological samples. However, the large size, structural flexibility, and complex structures of proteins hinder their efficient separation and analysis by conventional molecular imprinting technology. In this review, several novel molecular imprinting techniques, including surface imprinting, epitope imprinting, and metal chelate imprinting, are introduced. The emergence of these novel technologies has contributed to advances in protein analysis. The applications of these molecular imprinting techniques to the separation and analysis of proteins in the last three years are summarized herein. Finally, the promising future of molecular imprinting techniques in the area of proteins is prospected.

Key words: molecular imprinting, proteins, separation and determination, review

孙晓宇, 马润恬, 师彦平. 分子印迹技术在蛋白质分离分析中的研究进展[J]. 色谱, 2020, 38(1): 50-59.

SUN Xiaoyu, MA Runtian, SHI Yanping. Recent advances in molecular imprinting technology for the separation and analysis of proteins[J]. Chinese Journal of Chromatography, 2020, 38(1): 50-59.

图/表 7

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Analyte	Supports	Preparation method	Q/(mg/g)	IF	Reference
Q: adsorption capacity; IF: imprinting factor; Cyt C: cytochrome C; Con A: concanavalin A; HSA: human serum albumin; PMMA: poly(methyl methacrylate); -: no supports was used; /: the information was missing from the original reference.
Lys	glass substrate	surface imprinting	30.00	3.00	[38]
	Fe₃O₄/PMMA	surface imprinting	120.50	4.11	[39]
	Fe₃O₄@SiO₂	surface imprinting	124.30	3.20	[40]
	Fe₃O₄@SiO₂	surface imprinting	108.00	2.56	[41]
	MWCNTs	surface imprinting	418.00	4.10	[42]
BHb	Fe₃O₄@VTEO	surface imprinting	164.20	4.93	[31]
	Fe₃O₄@SiO₂	surface imprinting	84.50	3.95	[43]
	SiO₂	surface imprinting	90.30	3.10	[44]
	SiO₂	surface imprinting	67.70	5.00	[45]
	Fe₃O₄@SiO₂	surface imprinting	169.29	/	[46]
	Fe₃O₄@Au	surface imprinting	89.12	3.42	[47]
BSA	calcium alginate	surface imprinting	5.50	3.60	[48]
	SiO₂ particles	surface imprinting	162.82	3.03	[32]
	γ-Fe₂O₃	surface imprinting	300.00	4.00	[49]
	Fe₃O₄@void	surface imprinting	130.19	2.79	[34]
	Fe₃O₄@SiO₂	surface imprinting	147.00	2.90	[50]
	Fe₃O₄@IL	surface imprinting	50.60	3.33	[51]
Bromelain	mesoporous carbon	surface imprinting	135.96	2.16	[52]
Cyt C	-	metal chelate imprinting	86.47	3.48	[53]
	Fe₃O₄@SiO₂	epitope imprinting and surface imprinting	67.60	4.54	[54]
	cellulose nanofibers	metal chelate imprinting	208.40	8.20	[36]
Hb	SiO₂	epitope imprinting	/	/	[55]
	-	metal chelate imprinting	4.91	1.57	[56]
Con A	MCNTs	metal chelate imprinting	45.05	4.50	[35]
PSA	polystyrene core particles	epitope imprinting and surface imprinting	0.18	2.01	[57]
ADP-ribosylated proteins	silica gels	epitope imprinting	1917.50	2.60	[58]
HSA	MNCTs	surface imprinting, epitope imprinting and metal chelate imprinting	103.67	2.57	[59]

Analyte	Supports	Preparation method	Q/(mg/g)	IF	Reference
Q: adsorption capacity; IF: imprinting factor; Cyt C: cytochrome C; Con A: concanavalin A; HSA: human serum albumin; PMMA: poly(methyl methacrylate); -: no supports was used; /: the information was missing from the original reference.
Lys	glass substrate	surface imprinting	30.00	3.00	[38]
	Fe₃O₄/PMMA	surface imprinting	120.50	4.11	[39]
	Fe₃O₄@SiO₂	surface imprinting	124.30	3.20	[40]
	Fe₃O₄@SiO₂	surface imprinting	108.00	2.56	[41]
	MWCNTs	surface imprinting	418.00	4.10	[42]
BHb	Fe₃O₄@VTEO	surface imprinting	164.20	4.93	[31]
	Fe₃O₄@SiO₂	surface imprinting	84.50	3.95	[43]
	SiO₂	surface imprinting	90.30	3.10	[44]
	SiO₂	surface imprinting	67.70	5.00	[45]
	Fe₃O₄@SiO₂	surface imprinting	169.29	/	[46]
	Fe₃O₄@Au	surface imprinting	89.12	3.42	[47]
BSA	calcium alginate	surface imprinting	5.50	3.60	[48]
	SiO₂ particles	surface imprinting	162.82	3.03	[32]
	γ-Fe₂O₃	surface imprinting	300.00	4.00	[49]
	Fe₃O₄@void	surface imprinting	130.19	2.79	[34]
	Fe₃O₄@SiO₂	surface imprinting	147.00	2.90	[50]
	Fe₃O₄@IL	surface imprinting	50.60	3.33	[51]
Bromelain	mesoporous carbon	surface imprinting	135.96	2.16	[52]
Cyt C	-	metal chelate imprinting	86.47	3.48	[53]
	Fe₃O₄@SiO₂	epitope imprinting and surface imprinting	67.60	4.54	[54]
	cellulose nanofibers	metal chelate imprinting	208.40	8.20	[36]
Hb	SiO₂	epitope imprinting	/	/	[55]
	-	metal chelate imprinting	4.91	1.57	[56]
Con A	MCNTs	metal chelate imprinting	45.05	4.50	[35]
PSA	polystyrene core particles	epitope imprinting and surface imprinting	0.18	2.01	[57]
ADP-ribosylated proteins	silica gels	epitope imprinting	1917.50	2.60	[58]
HSA	MNCTs	surface imprinting, epitope imprinting and metal chelate imprinting	103.67	2.57	[59]

Analyte	Supports	Preparation method	Q/(mg/g)	IF	Reference
AHSG: alpha-2-Heremans-Schmid glycoprotein; IgG: immunoglobulin G; PGMA: poly(glycidyl methacrylate); PSG: poly(styrene-glycidyl methacrylate).
Trf	Fe₃O₄-NH₂	surface imprinting	2.62	17.47	[66]
	MCNTs	surface imprinting, epitope imprinting and metal chelate imprinting	68.48	2.17	[59]
OVA	Fe₃O₄@PGMA	surface imprinting	190.70	7.51	[63]
	GO	surface imprinting	278.00	9.5	[60]
	Fe₃O₄@VTEO	surface imprinting	81.20	2.28	[62]
	PSG NPs	metal chelate imprinting	138.92	4.44	[67]
	Fe₃O₄-NH₂	surface imprinting	/	3.86	[68]
	SiO₂	surface imprinting and metal chelate imprinting	243.40	4.82	[69]
Protein C	-	metal chelate imprinting	30.40	1.72	[30]
AHSG	Fe₃O₄@SiO₂	epitope imprinting	/	10.7	[61]
HRP	Fe₃O₄@SiO₂	epitope imprinting	/	10.7	[61]
	Fe₃O₄@SiO₂	surface imprinting	62.00	3.78	[70]
	Fe₃O₄@Au	surface imprinting	/	/	[64]
	Fe₃O₄-NH₂	surface imprinting	34.09	2.74	[68]
	Fe₃O₄@pTiO₂	surface imprinting	67.70	3.51	[65]
IgG	Fe₃O₄@Au	surface imprinting	33.2	/	[71]

Analyte	Supports	Preparation method	Q/(mg/g)	IF	Reference
AHSG: alpha-2-Heremans-Schmid glycoprotein; IgG: immunoglobulin G; PGMA: poly(glycidyl methacrylate); PSG: poly(styrene-glycidyl methacrylate).
Trf	Fe₃O₄-NH₂	surface imprinting	2.62	17.47	[66]
	MCNTs	surface imprinting, epitope imprinting and metal chelate imprinting	68.48	2.17	[59]
OVA	Fe₃O₄@PGMA	surface imprinting	190.70	7.51	[63]
	GO	surface imprinting	278.00	9.5	[60]
	Fe₃O₄@VTEO	surface imprinting	81.20	2.28	[62]
	PSG NPs	metal chelate imprinting	138.92	4.44	[67]
	Fe₃O₄-NH₂	surface imprinting	/	3.86	[68]
	SiO₂	surface imprinting and metal chelate imprinting	243.40	4.82	[69]
Protein C	-	metal chelate imprinting	30.40	1.72	[30]
AHSG	Fe₃O₄@SiO₂	epitope imprinting	/	10.7	[61]
HRP	Fe₃O₄@SiO₂	epitope imprinting	/	10.7	[61]
	Fe₃O₄@SiO₂	surface imprinting	62.00	3.78	[70]
	Fe₃O₄@Au	surface imprinting	/	/	[64]
	Fe₃O₄-NH₂	surface imprinting	34.09	2.74	[68]
	Fe₃O₄@pTiO₂	surface imprinting	67.70	3.51	[65]
IgG	Fe₃O₄@Au	surface imprinting	33.2	/	[71]

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分子印迹技术在蛋白质分离分析中的研究进展

Recent advances in molecular imprinting technology for the separation and analysis of proteins

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