基于不同配体的蛋白质纯化技术的研究与应用

doi:10.19586/j.2095-2341.2024.0153

生物技术进展 ›› 2025, Vol. 15 ›› Issue (1): 50-57.DOI: 10.19586/j.2095-2341.2024.0153

基于不同配体的蛋白质纯化技术的研究与应用

庞晓敏(), 李岩异()

华北制药金坦生物技术股份有限公司，石家庄 050035

收稿日期:2024-09-22 接受日期:2024-10-24 出版日期:2025-01-25 发布日期:2025-03-07
通讯作者: 李岩异
作者简介:庞晓敏E-mail: pxm15612772767@163.com；
基金资助:
河北重点研发计划项目(23372406D)

Research and Application of Protein Purification Technology Based on Different Ligands

Xiaomin PANG(), Yanyi LI()

North China Pharmaceutical Jintan Biotechnology Co. ，Ltd. ，Shijiazhuang 050035，China

Received:2024-09-22 Accepted:2024-10-24 Online:2025-01-25 Published:2025-03-07
Contact: Yanyi LI

摘要/Abstract

摘要：

蛋白质作为生命的物质基础，是生命活动的主要载体。针对下游工艺，不断开发出新的配体纯化技术，能够更安全、经济、高效地去除复杂蛋白质样品中的各种杂质。归纳了具有不同配体的介质材料（包括疏水配体、离子交换配体、混合模式配体和短肽仿生配体）和蛋白质分离技术（包括聚合物接枝技术和连续柱层析技术）的研究现状、创新应用及其发展前景，以期在蛋白质纯化过程中获取有效资源，为下游纯化技术发展提供参考。

关键词: 蛋白质纯化, 配体修饰, 混合模式配体, 聚合物接枝技术, 连续柱层析

Abstract:

As the material basis of life， proteins are the main carriers of life activities. For downstream processes， various impurities in complex protein samples can be removed more safely， economically， and efficiently for the continuous development of new ligand purification technologies. The research status， innovative applications and development prospects of medium materials with different ligands （including hydrophobic ligands， ion exchange ligands， mixed-mode ligands and short peptide biomimetic ligands） and protein separation technologies （including polymer grafting technology and continuous column chromatography technology） were summarized， which with the hope of obtaining effective resources in the protein purification process and providing a reference for the development of downstream purification technologies.

Key words: protein purification, ligand modification, mixed-mode ligand, polymer grafting technology, continuous column chromatography

中图分类号:

Q816

庞晓敏, 李岩异. 基于不同配体的蛋白质纯化技术的研究与应用[J]. 生物技术进展, 2025, 15(1): 50-57.

Xiaomin PANG, Yanyi LI. Research and Application of Protein Purification Technology Based on Different Ligands[J]. Current Biotechnology, 2025, 15(1): 50-57.

图/表 1

参考文献 62

1	HONDIUS D C, EIGENHUIS K N, MORREMA T H J, et al.. Proteomics analysis identifies new markers associated with capillary cerebral amyloid angiopathy in Alzheimer's disease[J/OL]. Acta Neuropathol. Commun., 2018, 6(1): 46[2024-10-15]. .
2	杨懿祺, 张志高, 游小龙, 等. 抗体药物的发展与应用[J]. 生物技术进展,2022,12(3): 358-365.
	YANG Y Q, ZHANG Z G, YOU X L, et al.. Development and application of monoclonal antibody-based drug[J]. Curr. Biotechnol., 2022, 12(3):358-365.
3	KITTLER S, EBNER J, BESLEAGA M, et al.. Recombinant protein L: production, purifcation and characterization of a universal binding ligand[J]. J. Biotechnol., 2022, 359: 108-115.
4	LIU S X, LI Z H, YU B, et al.. Recent advances on protein separation and purification methods[J/OL]. Adv. Colloid Interface Sci., 2020, 284: 102254 [2024-10-15]. .
5	SALIMI K, USTA D D, KOÇER İ, et al.. Protein A and protein A/G coupled magnetic SiO₂ microspheres for affinity purification of immunoglobulin G[J/OL]. Int. J. Biol. Macromol., 2018, 111: 178-185.
6	CHENG F, FENG Q C, HE W, et al.. Preparation and characterization of PEGylated thiophilic nanoparticles for rapid antibody separation[J]. Chin. J. Anal. Chem., 2018, 46(12): 1953-1960.
7	PRASANNA R R, KAMALANATHAN A S, VIJAYALAKSHMI M A. Development of L-histidine immobilized CIM(^®) monolithic disks for purification of immunoglobulin G[J]. J. Mol. Recognit., 2015, 28(3): 129-141.
8	WANG X Y, XIA D H, HAN H, et al.. Biomimetic small peptide functionalized affinity monoliths for monoclonal antibody purification[J]. Anal. Chim. Acta, 2018, 1017: 57-65.
9	HUANG H T, DONG X Y, SUN Y, et al.. Biomimetic affinity chromatography for antibody purification: host cell protein binding and impurity removal[J/OL]. J. Chromatogr. A, 2023, 1707: 464305[2024-10-15]. .
10	CHEN S T, WICKRAMASINGHE S R, QIAN X. Electrospun hydrophobic interaction chromatography (HIC) membranes for protein purification[J/OL]. Membranes, 2022, 12(7): 714[2024-10-15]. .
11	AOYAMA S, MATSUMOTO Y, MORI C, et al.. Application of novel mixed mode chromatography (MMC) resins having a hydrophobic modified polyallylamine ligand for monoclonal antibody purification[J/OL]. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2022, 1191: 123072[2024-10-15]. .
12	MORI C, IWAMOTO E, KADOI K, et al.. Impact of ligand structure and base bead pore size on host cell protein removal during monoclonal antibody purification using multimodal chromatography resin[J/OL]. J. Chromatogr. A, 2024, 1732: 465202[2024-10-15]. .
13	LIU J, LIU X, LIU Y, et al.. Pseudo-mercaptoethyl pyridine functionalized polyhedral oligomeric silsesquioxane-graphene composite via thiol-ene click reaction for highly selective purification of antibody[J/OL]. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2022, 1208: 123408[2024-10-15]. .
14	GUO M Y, YE J L, ZHENG C Y, et al.. Dual-recognition membrane Adsorbers combining hydrophobic charge-induction chromatography with surface imprinting via multicomponent reaction[J/OL]. J. Chromatogr. A, 2022, 1668: 462918[2024-10-15]. .
15	THAKHAM N, HUANG P H, LI K Y, et al.. Effect of delignification on the adsorption of loofah sponge-based immobilized metal affinity chromatography adsorbent for His-tagged trehalose synthase[J]. J. Biosci. Bioeng., 2024, 138(5): 445-451.
16	HAJIHASSAN Z, GHAEE A, BAZARGANNIA P, et al.. Affinity purification/immobilization of poly histidine-tagged proteins by nickel-functionalized porous chitosan membranes[J/OL]. J. Chromatogr. A, 2024, 1722: 464902[2024-10-15]. .
17	ZHANG X Y, CHEN J K, SHENG X Q, et al.. Preparation and characterization of a biomimetic honeycomb cross-linked chitosan membrane and its application in the serum of gastric cancer patients[J/OL]. Int. J. Biol. Macromol., 2024, 279: 135367[2024-10-15]. .
18	CUATRECASAS P, WILCHEK M. Single-step purifcation of avidine from egg white by afnity chromatography on biocytinSepharose columns[J]. Biochem. Biophys. Res. Commun., 1968, 33: 235-239.
19	彭晓燕, 陆盼盼, 胡祖权. 新型冠状病毒RBD蛋白原核表达及多克隆抗体的制备[J]. 生物技术进展, 2023,13(1):102-106.
	PENG X Y, LU P P, HU Z Q. Prokaryotic expression of the RBD protein of SARS-CoV-2 and its polyclonal antibodies preparation[J]. Curr. Biotechnol., 2023, 13(1): 102-106.
20	RODRIGUEZ E L, PODDAR S, IFTEKHAR S, et al.. Affinity chromatography: a review of trends and developments over the past 50 years[J/OL]. J. Infect. Public Health, 2020, 1157: 122332[2024-10-15]. .
21	ZARRINEH M, MASHHADI I S, FARHADPOUR M, et al.. Mechanism of antibodies purifcation by protein A[J/OL]. Anal. Biochem., 2020, 609: 113909[2024-09-22]. .
22	HAGEMANN F, ADAMETZ P, WESSLING M, et al.. Modeling hindered difusion of antibodies in agarose beads considering pore size reduction due to adsorption[J/OL]. J. Chromatogr. A, 2020, 1626: 461319[2024-09-22]. .
23	WANG Y, ZHANG X F, HAN N Y, et al.. Oriented covalent immobilization of recombinant protein A on the glutaraldehyde activated agarose support[J]. Int. J. Biol. Macromol., 2018, 120:100-108.
24	AGARWAL G, NAIK R R, STONE M O. Immobilization of histidine-tagged proteins on nickel by electrochemical dip pen nanolithography[J]. J. Am. Chem. Soc., 2003, 125(24): 7408-7412.
25	王海宁, 刘兴健, 高新桃, 等. SARS-CoV-2中和性纳米抗体的原核表达及中和活性检测[J]. 生物技术进展, 2022, 12(5):754-759.
	WANG H N, LIU X J, GAO X T, et al.. Prokaryotic expression and neutralization activity detection of SARS-CoV-2 neutralizing nanobody[J]. Curr. Biotechnol., 2022, 12(5): 754-759.
26	ZHENG H W, WEI F Y, TIAN J J, et al.. Preparation of nickel-chelated iminodiacetate-functionalized macroporous agarose monolith using modular and clickable building blocks for affinity separation of histidine-tagged recombinant proteins[J/OL]. J. Chromatogr. A, 2022, 1682: 463509[2024-10-15]. .
27	YUAN W M, ZHANG W J, MA F L, et al.. IFN-λ1 in CHO cells: its expression and biological activity[J/OL]. Cell Mol. Biol. Lett., 2017, 22: 26[2024-10-15]. .
28	REITER K, AGUILAR P P, WETTER V, et al.. Separation of virus-like particles and extracellular vesicles by flow-through and heparin affinity chromatography[J]. J. Chromatogr. A, 2019, 1588: 77-84.
29	PIETROCOLA G, RINDI S, NOBILE G, et al.. Purification of human plasma/cellular fibronectin and fibronectin fragments[J]. Meth. Mol. Biol. (Clifton N J), 2017, 1627: 309-324.
30	CHI H, TIAN S, LI X, et al.. Construction of lipid raft-coupled agarose gels as bioafnity chromatography materials and validation with tropomyosin-related kinase A-targeted drugs[J/OL]. J. Chromatogr. A., 2023, 1691:463803[2024-09-22]. .
31	HOU Z, HAN X, WANG Z, et al.. A terminal alkyne and disulfde functionalized agarose resin specifcally enriches azidohomoalanine labeled nascent proteins[J/OL]. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2021, 1165:122527 [2024-09-22]. .
32	KING C, PATEL R, PONNIAH G, et al.. Characterization of recombinant monoclonal antibody variants detected by hydrophobic interaction chromatography and imaged capillary isoelectric focusing electrophoresis[J]. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2018, 1085: 96-103.
33	RODLER A, BEYER B, UEBERBACHER R, et al.. Hydrophobic interaction chromatography of proteins: studies of unfolding upon adsorption by isothermal titration calorimetry[J]. J. Sep. Sci., 2018, 41(15): 3069-3080.
34	YANG Y X, CHEN Y C, YAO S J, et al.. Parameter-by-parameter estimation method for adsorption isotherm in hydrophobic interaction chromatography[J/OL]. J. Chromatogr. A, 2024, 1716:464638[2024-10-15]. .
35	EVANS C, MORIMITSU Y, NISHI R, et al.. Novel hydrophobically modifed agarose cryogels fabricated using dimethyl sulfoxide[J]. J. Biosci. Bioeng., 2022, 133(4):390-395.
36	CUMMINS P M, ROCHFORT K D, O'CONNOR B F. Ion-exchange chromatography: basic principles and application[J]. Meth. Mol. Biol. (Clifton N J), 2017, 1485: 209-223.
37	LOU Y, JI G R, LIU Q, et al.. Secretory expression and scale-up production of recombinant human thyroid peroxidase via baculovirus/insect cell system in a wave-type bioreactor[J]. Protein Expr. Purif., 2018, 149: 7-12.
38	SANCHEZ-REYES G, GRAALFS H, HAFNER M, et al.. Mechanistic modeling of ligand density variations on anion exchange chromatography[J]. J. Sep. Sci., 2021, 44(4): 805-821.
39	JING S Y, GOU J X, GAO D, et al.. Separation of monoclonal antibody charge variants using cation exchange chromatography: resins and separation conditions optimization[J]. Sep. Purif. Technol., 2020, 235: 116136.
40	HUANG C, WANG Y, XU X, et al.. Hydrophobic property of cation-exchange resins afects monoclonal antibody aggregation[J/OL]. J. Chromatogr. A, 2020, 1631: 461573[2024-09-22]. .
41	ROBERTS J A, KIMERER L, CARTA G. Efects of molecule size and resin structure on protein adsorption on multimodal anion exchange chromatography media[J/OL]. J. Chromatogr. A, 2020, 1628: 461444[2024-10-11]. .
42	LI M T, ZOU X J, ZHANG Q L, et al.. Binding mechanism of functional moieties of a mixed-mode ligand in antibody purification[J/OL]. Chem. Eng. J., 2020, 400: 125887[2024-10-15]. .
43	GU J L, PI W Y, XIE W F, et al.. Improved antibody adsorption performance of phenylbased mixed-mode adsorbents by adjusting the functional group of ligand[J/OL]. Biochem. Eng. J., 2021, 176: 108092[2024-09-22]. .
44	LI M, LIN D, YAO S, et al.. Study on antibody adsorption and elution performance of carboxyl and hydrophobic groups on mixed-mode ligands[J]. J. Sep. Sci., 2022, 45(15): 2946-2955.
45	AOYAMA S, MATSUMOTO Y, MORI C, et al.. Application of novel mixed mode chromatography (MMC) resins having a hydrophobic modified polyallylamine ligand for monoclonal antibody purification[J/OL]. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2022, 1191: 123072[2024-10-15]. .
46	SHI W, ZHANG T Y, FANG C Y, et al.. Transforming waste into valuables: preparation and evaluation of dual-ligand hydrophobic charge-induction chromatography using two poor performing ligands[J/OL]. J. Chromatogr. A, 2024, 1726: 464975[2024-10-15]. .
47	YE J L, ZHANG Y F, MENG J Q. Protein-ligand interactions for hydrophobic charge-induction chromatography:a QCM-D study[J/OL]. Appl. Surf. Sci., 2022, 572: 151420[2024-10-15]. .
48	FANG Y M, LIN D Q, YAO S J. Review on biomimetic afnity chromatography with short peptide ligands and its application to protein purification[J]. J. Chromatogr. A, 2018, 1571: 1-15.
49	ZOU X J, ZHANG Q L, LU H L, et al.. Development of a hybrid biomimetic ligand with high selectivity and mild elution for antibody purification[J]. Chem. Eng. J., 2019, 368: 678-686.
50	FANG Y M, CHEN S G, LIN D Q, et al.. A new tetrapeptide biomimetic chromatographic resin for antibody separation with high adsorption capacity and selectivity[J/OL]. J. Chromatogr. A, 2019, 1604: 460474[2024-10-15]. .
51	FANG Y M, ZHANG Q L, LIN D Q, et al.. One kind of challenging tetrapeptide biomimetic chromatographic resin for antibody separation[J/OL]. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2022, 1208: 123407[2024-10-15]. .
52	FANG Y M, ZHU H Y, LIN D Q, et al.. A novel dextrangrafted tetrapeptide resin for antibody purification[J]. J. Sep. Sci., 2018, 43(19): 3816-3823.
53	HAO D X, ZHANG R Y, GE J, et al.. Rapid and high-capacity loading of IgG monoclonal antibodies by polymer brush and peptides functionalized microspheres[J/OL]. J. Chromatogr. A, 2021, 1640: 461948[2024-10-15]. .
54	GU J L, ZHANG Y, TONG H F, et al.. Preparation and evaluation of dextran-grafted mixed-mode chromatography adsorbents[J]. J. Chromatogr. A, 2019, 1599: 1-8.
55	QIAO L Z, DU Y C, DU K F. Grafting diethylaminoethyl dextran to macroporous cellulose microspheres:a protein anion exchanger of high capacity and fast uptake rate[J]. Sep. Purif. Technol., 2022, 297: 121434.
56	YANG O, PRABHU S, IERAPETRITOU M. Comparison between batch and continuous monoclonal antibody production and economic analysis[J]. Ind. Eng. Chem. Res., 2019, 58(15): 5851-5863.
57	CAPITO F, FLATO H, OEINCK V, et al.. Mimicking continuous capture chromatography for virus clearance using a single chromatography column model[J/OL]. Biotechnol. J., 2022, 17(5): e2100433[2024-10-15]. .
58	MATOS T, HOYING D, KRISTOPEIT A, et al.. Continuous multi-membrane chromatography of large viral particles[J/OL]. J. Chromatogr. A, 2023, 1705: 464194[2024-10-15]. .
59	LUO Y D, ZHANG Q L, YAO S J, et al.. Evaluation of adsorption selectivity of immunoglobulins M, A and G and purification of immunoglobulin M with mixed-mode resins[J]. J. Chromatogr. A, 2018, 1533: 77-86.
60	SUN Y N, SHI C, ZHANG Q L, et al.. Comparison of protein A afnity resins for twin-column continuous capture processes: process performance and resin characteristics[J/OL]. J. Chromatogr. A, 2021, 1654:462454[2024-09-22]. .
61	SUN Y N, SHI C, ZHONG X Z, et al.. Model-based evaluation and model-free strategy for process development of three-column periodic counter-current chromatography[J]. J. Chromatogr. A, 2022, 1677: 463311[2024-10-15]. .
62	SHI C, GAO Z Y, ZHANG Q L, et al.. Model-based process development of continuous chromatography for antibody capture:a case study with twin-column system[J]. J. Chromatogr. A, 2020, 1619: 460936[2024-10-15]. .

配体类型	配体名称	基架	作用机制	应用	参考文献
亲和配体	蛋白A	醛基功能化二氧化硅微球	提供较大的表面积，结合容量	从兔血清中分离IgG的纯度高于95%	[5]
	甲氧基聚乙二醇2000-氨基	磁性纳米颗粒	中和pH和盐浓度对IgG选择性的影响	从胎牛血清中分离IgG的纯度96%；从细胞培养上清液中分离奥马珠单抗的纯度为99%	[6]
	L-His	环氧基、羰基二咪唑和乙二胺整体柱	排除流速对结合容量的影响，发挥组氨酸柱的稳定性和可重复使用性，实现对抗体的高通量纯化	IgG最大吸附量分别为12.11±0.17、15.85±0.18和 19.83±0.25 mg·mL^-1	[7]
仿生肽配体	3,5-二-叔丁基-4-羟基苯甲酸-精氨酸-精氨酸-甘氨酸	功能化的整体柱	发挥整体柱高孔隙率和可及性，提供更高的动态结合容量	从生物样品中纯化曲妥珠单抗或hIgG，动态结合容量高达34.6 mg·mL^-1	[8]
仿生肽配体	FYWHCLDE	琼脂糖凝胶6FF	减少由HCP引起的单克隆抗体聚集	单克隆抗体回收率高于68.7%	[9]
疏水配体	聚（N-乙烯基己内酰胺）	再生纤维素纳米纤维	发挥粗纤维和更开放孔隙结构，提供更高的结合容量	可实现约25 mg·mL^-1的静态结合容量和超过30 mg·mL^-1的动态结合容量	[10]
疏水配体	丁基或苯基修饰的聚烯丙胺	疏水改性的高度交联纤维素珠	疏水基团的结构影响单克隆抗体的产率	直接与特定的阳离子交换色谱步骤联用，实现单克隆抗体产率>93%	[11]
混合模式配体	环氧氯丙烷、高碘酸钠、二乙烯基砜	纤维素微珠	发挥非芳香族部分配体结构具有的较强的HCP去除能力	可将HCP水平降低3个数量级以提高单克隆抗体精制过程中的宿主杂质去除率	[12]
疏水电荷诱导配体	4-乙烯基吡啶	新型石墨烯复合材料	抑制共存蛋白质在石墨烯基底上的非特异性吸附	对IgG表现出高选择性。pH 7.4时，IgG吸附效率达90%，吸附容量为500 mg·g⁻¹	[13]
疏水电荷诱导配体	β-吲哚基乙胺	再生纤维素	保留介质pH依赖性和耐盐性	有效地混合溶液中分离纯度为88%的IgG	[14]
固化离子配体	CO²⁺	基于丝瓜络海绵的吸附剂	脱木质素处理提高吸附容量和选择性	对重组组氨酸标签海藻糖合酶的最大吸附容量为2.04±0.14 mg·g^-1，比对照提高73%	[15]
	Ni²⁺	多孔壳聚糖膜	发挥多孔壳聚糖膜高孔隙率镍吸附量的优势	对带有组氨酸标签尾的重组β-神经生长因子（β-NGF）进行纯化，纯度超过78%	[16]
	Ti⁴⁺	仿生蜂窝状壳聚糖膜	提供良好的亲水性和更好的生物相容性	用于富集人体血清中的磷酸肽，从而用于研究基因本体分析、胃癌患者的生物过程、细胞组分和分子功能	[17]

配体类型	配体名称	基架	作用机制	应用	参考文献
亲和配体	蛋白A	醛基功能化二氧化硅微球	提供较大的表面积，结合容量	从兔血清中分离IgG的纯度高于95%	[5]
	甲氧基聚乙二醇2000-氨基	磁性纳米颗粒	中和pH和盐浓度对IgG选择性的影响	从胎牛血清中分离IgG的纯度96%；从细胞培养上清液中分离奥马珠单抗的纯度为99%	[6]
	L-His	环氧基、羰基二咪唑和乙二胺整体柱	排除流速对结合容量的影响，发挥组氨酸柱的稳定性和可重复使用性，实现对抗体的高通量纯化	IgG最大吸附量分别为12.11±0.17、15.85±0.18和 19.83±0.25 mg·mL^-1	[7]
仿生肽配体	3,5-二-叔丁基-4-羟基苯甲酸-精氨酸-精氨酸-甘氨酸	功能化的整体柱	发挥整体柱高孔隙率和可及性，提供更高的动态结合容量	从生物样品中纯化曲妥珠单抗或hIgG，动态结合容量高达34.6 mg·mL^-1	[8]
仿生肽配体	FYWHCLDE	琼脂糖凝胶6FF	减少由HCP引起的单克隆抗体聚集	单克隆抗体回收率高于68.7%	[9]
疏水配体	聚（N-乙烯基己内酰胺）	再生纤维素纳米纤维	发挥粗纤维和更开放孔隙结构，提供更高的结合容量	可实现约25 mg·mL^-1的静态结合容量和超过30 mg·mL^-1的动态结合容量	[10]
疏水配体	丁基或苯基修饰的聚烯丙胺	疏水改性的高度交联纤维素珠	疏水基团的结构影响单克隆抗体的产率	直接与特定的阳离子交换色谱步骤联用，实现单克隆抗体产率>93%	[11]
混合模式配体	环氧氯丙烷、高碘酸钠、二乙烯基砜	纤维素微珠	发挥非芳香族部分配体结构具有的较强的HCP去除能力	可将HCP水平降低3个数量级以提高单克隆抗体精制过程中的宿主杂质去除率	[12]
疏水电荷诱导配体	4-乙烯基吡啶	新型石墨烯复合材料	抑制共存蛋白质在石墨烯基底上的非特异性吸附	对IgG表现出高选择性。pH 7.4时，IgG吸附效率达90%，吸附容量为500 mg·g⁻¹	[13]
疏水电荷诱导配体	β-吲哚基乙胺	再生纤维素	保留介质pH依赖性和耐盐性	有效地混合溶液中分离纯度为88%的IgG	[14]
固化离子配体	CO²⁺	基于丝瓜络海绵的吸附剂	脱木质素处理提高吸附容量和选择性	对重组组氨酸标签海藻糖合酶的最大吸附容量为2.04±0.14 mg·g^-1，比对照提高73%	[15]
	Ni²⁺	多孔壳聚糖膜	发挥多孔壳聚糖膜高孔隙率镍吸附量的优势	对带有组氨酸标签尾的重组β-神经生长因子（β-NGF）进行纯化，纯度超过78%	[16]
	Ti⁴⁺	仿生蜂窝状壳聚糖膜	提供良好的亲水性和更好的生物相容性	用于富集人体血清中的磷酸肽，从而用于研究基因本体分析、胃癌患者的生物过程、细胞组分和分子功能	[17]

基于不同配体的蛋白质纯化技术的研究与应用

Research and Application of Protein Purification Technology Based on Different Ligands

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 62

相关文章 1

编辑推荐

Metrics

本文评价