Corresponding Author

Gen-Xi LI(genxili@nju.edu.cn)


Protein post-translational modification is a key physiological procedure, which has received more and more research interests from the scientists not only in protein science but also in some other fields. The usually employed techniques for the study of protein modification include mass spectrum, affinity chromatography, etc. Considering the complexity of protein modification and the urgent demand of such kind of study, it is highly required to develop new techniques to perform more studies. Electrochemical methods, which have been widely used in chemical study and analysis, are playing an increasingly important role in many fields of biological studies. The modification of protein may induce chemical changes of specific groups, which may be characterized by using electrochemical methods via various approaches. Therefore, the changes of protein structure and function through protein modification can be revealed and the enzyme activity involved in protein modification may be detected rapidly, sensitively and accurately by taking the advantages of electrochemical methods, and consequently more and more achievements have been obtained. Based on some recent studies in the group of the authors and also some interesting works of other groups, this article reviews the progress of electrochemical study on protein modification, so as to exchange the research ideas with the colleagues in electrochemical community and some others related to protein science.

Graphical Abstract


protein modification, protein electrochemistry, bioelectrochemistry, electrochemistry

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[1] Appel R D, Bairoch A. Post-translational modifications: A challenge for proteomics and bioinformatics [J]. Proteomics, 2004, 4(6): 1525-15261.

[2] Mann M, Jensen O N. Proteomic analysis of post-translational modifications [J]. Nature Biotechnology, 2003, 21(3): 255-261.

[3] Seo J, Lee K J. Post-translational modifications and their biological functions: proteomic analysis and systematic approaches [J]. Journal of Biochemistry and Molecular Biology, 2004, 37(1): 35-44.

[4] Fan C H, Wang H Y, Sun S, et al. Electron transfer reactivity and enzymatic activity of hemoglobin in a SP sephadex membrane [J]. Analytical Chemistry, 2001, 73(13): 2850-2854.

[5] Zhou H, Gan X, Wang J, et al. Hemoglobin-based hydrogen peroxide biosensor tuned by the photovoltaic effect of nano titanium dioxide [J]. Analytical Chemistry, 2005, 77(18): 6102-6104.

[6] Zhang W J, Huang Y X, Dai H, et al. Tuning the redox and enzymatic activity of glucose oxidase in layered organic films and its application in glucose biosensors [J]. Analytical Biochemistry, 2004, 329(1): 85-90.

[7] Shen M, Wang J, Yang M, et al. Direct electrochemistry of the Ti(IV)-transferrin complex: Probing into the transport of Ti(IV) by human serum transferring [J]. Electrochemistry Communications, 2011, 13(2): 114-116.

[8] Wang J, Liang Z Q, Wang L H, et al. Electron transfer reactivity and catalytic activity of structurally rigidized hemoglobin [J]. Sensors and Actuators B: Chemical, 2007, 125(1): 17-21.

[9] Li G X. Protein-based voltammetric sensors [M]//Grimes C A, Dickey E C, Pishko M V (Eds.). Encyclopedia of sensors, Volume 8. Stevenson Ranch: American Scientific Publishers, 2006: 301-313.

[10] Li G X. Protein-based biosensors using nanomaterials [M]//Kumar C (Eds.). Nanotechnologies for life sciences, Volume 8. New York: Wiley-VCH, 2007: 278-310.

[11] Li G X. Heme protein-based electrochemical biosensors [M]//Kadish K M, Smith K M, Guilard R (Eds.). Handbook of porphyrin science, Volume 5. Singapore: World Scientific Publishing, 2010: 203-298.

[12] LI G X (李根喜). Electrochemical study of protein enzyme [J]. Journal of Shanghai University (Natural Science) (上海大学学报(自然科学版)), 2011, 17(4): 567-572.

[13] Xiao H, Zhou H, Chen G F, et al. Interaction between inducible nitric oxide synthase and calmodulin in Ca2+-free and -bound forms [J]. Journal of Proteome Research, 2007, 6(4): 1426-1429.

[14] Zhang K, Zhu X L, Wang J, et al. Strategy to fabricate an electrochemical aptasensor: application to the assay of adenosine deaminase activity [J]. Analytical Chemistry, 2010, 82(8): 3207-3211.

[15] Xiao H, Liu L, Meng F B, et al. Electrochemical approach to detect apoptosis [J]. Analytical Chemistry, 2008, 80(13): 5272-5275.

[16] Liu T, Zhu W, Yang X, et al. Detection of apoptosis based on the interaction between annexin V and phosphatidylserine [J]. Analytical Chemistry, 2009, 81(6): 2410-2413.

[17] Yang Q L, Zhao J, Zhou N D, et al. Electroanalysis of telomere-bending motions caused by hTRF1 [J]. Biosensors and Bioelectronics, 2011, 26(5): 2228-2231.

[18] Huang Y X, Liu L, Shi C, et al. Electrochemical analysis of the effect of Ca2+ on cardiolipin-cytochrome c interaction [J]. Biochimica et Biophysica Acta, 2006, 1760(12): 1827-1830.

[19] Yang R, Gao G, Liu T, et al. Enhanced ability of hemoglobin to carry oxygen by salidroside [J]. Electrochemistry Communications, 2007, 9(1): 94-96.

[20] Xiao H, Wang J, Chen G F, et al. Electrochemical evaluation of self-disassociatio n of PKA upon activation by cAMP [J]. Langmuir, 2007, 23(7): 3506-3508.

[21] Huang J Y, Chen L, Zhang X, et al. Electrochemical studies of ion-channel behavior of annexin V in phosphatidylcholine bilayer membranes [J]. Electrochemistry Communications, 2008, 10(3): 451-454.

[22] Liang X Q, Chen G F, Zhang X, et al. Study of UVA irradiation on hemoglobin in the presence of NADH [J]. Journal of Photochemistry and Photobiology B: Biology, 2008, 90(1): 53-56.

[23] Wang J, Cao Y, Chen G F, et al. Regulation of thrombin activity with a bifunctional aptamer and hemin: development of a new anticoagulant and antidote pair [J]. ChemBioChem, 2009, 10(13): 2171-2176.

[24] Zhou N D, Cao Y, Li G X. Electron transfer and interfacial behavior of redox proteins [J]. Science China Chemistry, 2010, 53(4): 720-736.

[25] Liu X J, Huang Y X, Zhang W J, et al. Electrochemical investigation of redox thermodynamics of immobilized myoglobin: ionic and ligation effects [J]. Langmuir, 2005, 21(1): 375-378.

[26] Huang J Y, Zhang D M, Xing W, et al. An approach to assay th e enzymatic activity of calcineurin and the inhibitory effect of zinc ion [J]. Analytical Biochemistry, 2008, 375(2): 385-387.

[27] Cao Y, Wang J, Xu Y, et al. Combination of enzyme catalysis and electrocatalysis for biosensor fabrication: application to assay the activity of indoleamine 2, 3-dioxygensae [J]. Biosensors and Bioelectronics, 2010, 26(1): 87-91.

[28] Miao P, Ning L, Li X, et al. An electrochemical alkaline phosphatase biosensor fabricated with two DNA probes coupled with λ exonuclease [J]. Biosensors and Bioelectronics, 2011, 27(1): 178-182.

[29] Cao Y, Jing W, Xu Y Y, et al. Sensing purine nucleoside phosphorylase activity by using silver nanoparticles [J]. Biosensors and Bioelectronics, 2010, 25(5): 1032-1036.

[30] Shao Z Y, Liu Y X, Xiao H, et al. PCR-free electrochemical assay of telomerase activity [J]. Electrochemistry Communications, 2008, 10(10): 1502-1504.

[31] Manning G, Whyte D B, Martinez R, et al. The protein kinase complement of the human genome [J]. Science, 2002, 298(5600): 1912-1934.

[32] Cohen P. Protein kinases-the major drug targets of the twenty-first century? [J] Nature Reviews Drug Discovery, 2002, 1(4): 309-315.

[33] Wang J, Shen M, Cao Y, et al. Switchable “on-off” electrochemical technique for detection of phosphorylation [J]. Biosensors and Bioelectronics, 2010, 26(2): 38-642.

[34] Yang Y, Guo L H, Qu N, et al. Label-free electrochemical measurement of protein tyrosine kinase activity and inhibition based on electro-catalyzed tyrosine signaling [J]. Biosensors and Bioelectronics, 2011, 28(1): 284-290.

[35] Xu X, Nie Z, Chen J, et al. A DNA-based electrochemical strategy for label-free monitoring the activity and inhibition of protein kinase [J]. Chemical Communications, 2009, 45: 6946-6948.

[36] Wang J, Cao Y, Li Y, et al. Electrochemical strategy for detection of phosphorylation based on enzyme-linked electrocatalysis [J]. Journal of Electroanalytical Chemistry, 2011, 656 (1/2): 274-278.

[37] Song H, Kerman K, Kraatz H. Electrochemical detection of kinase-catalyzed phosphorylation using ferrocene-conjugated ATP [J]. Chemical Communications, 2008, 44(4): 502-504.

[38] Beckett D. Biotin sensing at the Molecular Level [J]. Journal of Nutrition, 2009, 139(1): 167-170.

[39] Ng B, Polyak S W, Bird D, et al. Escherichia coli biotin protein ligase: characterization and development of a high-throughput assay [J]. Analytical Biochemistry, 2008, 376(1): 131-136.

[40] Wang Z Y, Liu L, Xu Y Y, et al. Simulation and assay of protein biotinylation with electrochemical technique [J]. Biosensors and Bioelectronics, 2011, 26(11): 4610- 4613.

[41] Du D, Wang L, Shao Y, et al. Functionalized graphene oxide as a nanocarrier in a multienzyme labeling amplification strategy for ultrasensitive electrochemical immunoassay of phosphorylated p53 (S392) [J]. Analytical Chemistry, 2011, 83(3): 746-752.

[42] Tully E, Higson S P, O’Kennedy R. The development of a ‘labeless’ immunosensor for the detection of Listeria monocytogenes cell surface protein, Internalin B [J]. Biosensors and Bioelectronics, 2008, 23(6): 906-912.

[43] Shi X W, Liu Y, Lewandowski A T, et al. Chitosan biotinylation and electrodeposition for selective protein assembly [J]. Macromolecular Bioscience, 2008, 8(5): 451-457.

[44] Huang X, Du D, Gong X J, et al. Composite assembly of silver nanoparticles with avidin and biotinylated AChE on gold for the pesticidal electrochemical sensing [J]. Electroanalysis, 2008, 20(4): 402- 409.
[45] Vidal J C, Bonel L, Duato P, et al. Improved electrochemical competitive immunosensor for ochratoxin A with a biotinylated monoclonal antibody capture probe and colloidal gold nanostructuring [J]. Analytical Methods, 2011, 3(4): 977-984.
[46] Zhang J J, Zheng T T, Cheng F F, et al. Electrochemical sensing for caspase 3 activity and inhibition using quantum dot functionalized carbon nanotube labels [J]. Chemical Communications, 2011, 47(4): 1178-1180.
[47] LI J (李 军), DU X (杜 鑫), Hosseini Moghaddam S H, et al. The research progress in protein glycosylation modification [J]. Bulletin of Science and Technology (科技通报), 2009, 25(6): 773-783.
[48] Suzuki K, Yagi K, Oka R, et al. Relationships of serum haptoglobin concentration with HbA1c and glycated albumin concentrations in Japanese type 2 diabetic patients [J]. Clinical Chemistry and Laboratory Medicine, 2009, 47(1): 70-74.
[49] Yang J H, Zhao J, Xiao H, et al. Study of hemoglobin and human serum albumin glycation with electrochemical techniques [J]. Electroanalysis, 2011, 23(2): 463 - 468.
[50] Nicoletti F, Howes B, Fittipaldi M, et al. Ibuprofen induces an allosteric conformational transition in the heme complex of human serum albumin with significant effects on heme ligation [J]. Journal of the American Chemical Society, 2008, 130(35): 11677-11688.
[51] Adamczyk M, Chen Y Y, Johnson D D, et al. Chemiluminescent acridinium-9-carboxamide boronic acid probes: application to a homogeneous glycated hemoglobin assay [J]. Bioorganic & Medicinal Chemistry, 2006, 16(5): 1324-1328.
[52] Nathan D M, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time [J]. Diabetologia, 2007, 50(11): 2239-2244.
[53] Park J Y, Chang B Y, Nam H, et al. Selective electrochemical sensing of glycated hemoglobin (HbA1c) on thiophene-3-boronic acid self-assembled monolayer covered gold electrodes [J]. Analytical Chemistry, 2008, 80(21): 8035-8044.
[54] Song S Y, Yoon H C. Boronic acid-modi?ed thin ?lm interface for speci?c binding of glycated hemoglobin (HbA1c) and electrochemical biosensing [J]. Sensors and Actuators B: Chemical, 2009, 140(1): 233-239.
[55] Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: An independent risk factor for vascular disease [J]. The New England Journal of Medicine, 1991, 324(17): 1149-1155.
[56] Yang X, Gao Y, Zhou J. Plasma homocysteine thiolactone adducts associated with risk of coronary heart disease [J]. Clinica Chimica Acta, 2006, 364(1/2): 230-234.
[57] Per?a-Kaján J, Twardowski T, Jakubowski H. Mechanisms of homocysteine toxicity in humans [J]. Amino Acids, 2007, 32(4): 561-572.
[58] Jakubowski H. Pathophysiological consequences of homocysteine excess [J]. The Journal of Nutrition, 2006, 136(6 Suppl): 1741S-1749S.
[59] Per?a-Kaján J, Marczak ?, Kaján L, et al. Modification by homocysteine thiolactone affects redox status of cytochrome c [J]. Biochemistry, 2007, 46(21): 6225-6231.
[60] Zhao J, Zhu W, Liu T, et al. Electrochemical probing into cytochrome c modification with homocysteine-thiolactone [J]. Analytical and Bioanalytical Chemistry, 2010, 397(2): 695-701.



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