生物正交标记反应研究进展

doi:10.6023/A15030214

摘要/Abstract

对活体生物大分子进行特异性标记是一项具有挑战性的工作, 它要求这类化学反应能够在生理条件下高效特异地进行, 不会与生物体系中存在的各种活性物质发生副反应. 最近十几年开发的生物正交反应能够比较好地满足这些要求, 它们在生物分子标记方面的应用拓展了我们对细胞内生物体系的理解. 主要介绍那些应用广泛且可以用于活体细胞标记的生物正交反应. 重点介绍通过位点特异性引入生物正交官能团来进行选择性标记细胞内目标蛋白质的策略. 同时, 我们根据使用催化剂类型对这些生物正交反应进行分类, 并且列表比较它们的差异, 以便于研究者挑选合适的反应. 最后对生物正交反应的开发和进一步应用进行了展望.

关键词: 生物正交反应, 活体细胞, 蛋白质标记, 位点特异性, 非天然氨基酸

Selective labeling of biomolecules inside living cells is a challenging task, which requires the reaction to proceed efficiently and selectively under physiological condition without interfering with active species presented in the living systems. Bioorthogonal reactions, which were developed in the past decade, successfully meet these requirements and their applications in biomolecule labeling have expanded our understanding of cellular process. Considerable attention has been focused on the optimization of a few known bioorthogonal reactions, including discovery of new ligands and privileged substrates for transition metal catalyzed reactions, and the use of strain promoted functional group for substrate activation in the cycloaddition reactions. In addition, new bioorthogonal reactions, including the fluorogenic reactions, have also been emerged in the past few years. Progress has also been made toward the development of mutually exclusive bioorthogonal reactions and their application for multiple labeling of biomolecules inside living cells. Here we review the most widely used bioorthogonal labeling reactions, drawing particular attention to those that have been used in living systems. We focused on the selective labeling of target proteins by means of site-specific introduction of a functional group followed by the bioorthogonal reaction with a complementary functional group. We categorized these reactions into three different groups based on the catalysts used in the reactions: metal catalyzed reactions, photo induced reactions and reactions without catalyst. The biological applications of these bioorthogonal reactions have also been briefly introduced. We also listed the rate constants and main references of these reactions to facilitate researchers for choosing the appropriate one. Lastly, we highlight ongoing challenges in developing new bioorthogonal reactions and their application to study complex biological systems.

Key words: bioorthogonal reaction, living cells, protein labeling, site-specific, unnatural amino acid

引用此文

杨麦云, 陈鹏. 生物正交标记反应研究进展[J]. 化学学报, 2015, 73(8): 783-792.

Yang Maiyun, Chen Peng R.. Progress in the Bioorthogonal Labeling Reactions[J]. Acta Chim. Sinica, 2015, 73(8): 783-792.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

参考文献

[1] Prescher, J. A.; Bertozzi, C. R. Nat. Chem. Biol. 2005, 1, 13.
[2] (a) Nienhaus, G. U. Angew. Chem. Int. Ed. 2008, 47, 8992.
(b) Tsien, R. Y. Angew. Chem., Int. Ed. 2009, 48, 5612.
[3] (a) Sletten, E. M.; Bertozzi, C. R. Angew. Chem., Int. Ed. 2009, 48, 6974.
(b) Lim, R. K. V.; Lin, Q. Chem. Commun. 2010, 46, 1589.
(c) Grammel, M.; Hang, H. C. Nat. Chem. Biol. 2013, 9, 475.
(d) Zhang, Y.; Chen, P. R.; Yao, Z. Chin. Sci. Bull. (Chin Ver) 2013, 58, 2872. (张艳, 陈鹏, 姚祝军, 科学通报, 2013, 58, 2872.)
[4] (a) Chen, I.; Howarth, M.; Lin, W.; Ting, A. Y. Nat. Meth. 2005, 2, 99.
(b) Wu, P.; Shui, W.; Carlson, B. L.; Hu, N.; Rabuka, D.; Lee, J.; Bertozzi, C. R. Proc. Natl. Acad. Sci. USA 2009, 106, 3000.
(c) Ramil, C. P.; Lin, Q. Chem. Commun. 2013, 49, 11007.
(d) Li, J.; Wang, J.; Chen, P. R. Acta Chim. Sinica 2012, 70, 1439. (李劼, 王杰, 陈鹏, 化学学报, 2012, 70, 1439.)
(e) Wang, Y.; Ye, X. Acta Chim. Sinica 2012, 70, 2208. (王玥, 叶新山, 化学学报, 2012, 70, 2208.)
[5] Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004.
[6] Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596.
[7] Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057.
[8] (a) Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radi?, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 1053.
(b) Lewis, W. G.; Magallon, F. G.; Fokin, V. V.; Finn, M. G. J. Am. Chem. Soc. 2004, 126, 9152.
(c) Presolski, S. I.; Hong, V.; Cho, S.-H.; Finn, M. G. J. Am. Chem. Soc. 2010, 132, 14570.
[9] (a) Song, C.-X.; Szulwach, K. E.; Dai, Q.; Fu, Y.; Mao, S.-Q.; Lin, L.; Street, C.; Li, Y.; Poidevin, M.; Wu, H.; Gao, J.; Liu, P.; Li, L.; Xu, G.-L.; Jin, P.; He, C. Cell 2013, 153, 678.
(b) Charron, G.; Li, M. M.; MacDonald, M. R.; Hang, H. C. Proc. Natl. Acad. Sci. USA 2013, 110, 11085.
(c) Hong, V.; Steinmetz, N. F.; Manchester, M.; Finn, M. G. Bioconjugate Chem. 2010, 21, 1912.
[10] Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210.
[11] Rodionov, V. O.; Fokin, V. V.; Finn, M. G. Angew. Chem., Int. Ed. 2005, 44, 2210.
[12] Worrell, B. T.; Malik, J. A.; Fokin, V. V. Science 2013, 340, 457.
[13] Chan, T. R.; Hilgraf, R.; Sharpless, K. B.; Fokin, V. V. Org. Lett. 2004, 6, 2853.
[14] Link, A. J.; Tirrell, D. A. J. Am. Chem. Soc. 2003, 125, 11164.
[15] Hong, V.; Presolski, S. I.; Ma, C.; Finn, M. G. Angew. Chem., Int. Ed. 2009, 48, 9879.
[16] Besanceney-Webler, C.; Jiang, H.; Zheng, T.; Feng, L.; Soriano del Amo, D.; Wang, W.; Klivansky, L. M.; Marlow, F. L.; Liu, Y.; Wu, P. Angew. Chem., Int. Ed. 2011, 50, 8051.
[17] Soriano del Amo, D.; Wang, W.; Jiang, H.; Besanceney, C.; Yan, A. C.; Levy, M.; Liu, Y.; Marlow, F. L.; Wu, P. J. Am. Chem. Soc. 2010, 132, 16893.
[18] Wang, W.; Hong, S.; Tran, A.; Jiang, H.; Triano, R.; Liu, Y.; Chen, X.; Wu, P. Chem. Asian J. 2011, 6, 2796.
[19] Kennedy, D. C.; McKay, C. S.; Legault, M. C. B.; Danielson, D. C.; Blake, J. A.; Pegoraro, A. F.; Stolow, A.; Mester, Z.; Pezacki, J. P. J. Am. Chem. Soc. 2011, 133, 17993.
[20] (a) Yang, M.; Song, Y.; Zhang, M.; Lin, S.; Hao, Z.; Liang, Y.; Zhang, D.; Chen, P. R. Angew. Chem., Int. Ed. 2012, 51, 7674.
(b) Yang, M.; Jalloh, A. S.; Wei, W.; Zhao, J.; Wu, P.; Chen, P. R. Nat. Commun. 2014, 5.
[21] Brotherton, W. S.; Michaels, H. A.; Simmons, J. T.; Clark, R. J.; Dalal, N. S.; Zhu, L. Org. Lett. 2009, 11, 4954.
[22] Uttamapinant, C.; Tangpeerachaikul, A.; Grecian, S.; Clarke, S.; Singh, U.; Slade, P.; Gee, K. R.; Ting, A. Y. Angew. Chem., Int. Ed. 2012, 51, 5852.
[23] Yang, Y.; Lin, S.; Lin, W.; Chen, P. R. ChemBioChem 2014, 15, 1738.
[24] Jiang, H.; Zheng, T.; Lopez-Aguilar, A.; Feng, L.; Kopp, F.; Marlow, F. L.; Wu, P. Bioconjugate Chem. 2014, 25,698.
[25] Chalker, J. M.; Wood, C. S. C.; Davis, B. G. J. Am. Chem. Soc. 2009, 131, 16346.
[26] Li, N.; Lim, R. K. V.; Edwardraja, S.; Lin, Q. J. Am. Chem. Soc. 2011, 133, 15316.
[27] Spicer, C. D.; Triemer, T.; Davis, B. G. J. Am. Chem. Soc. 2012, 134, 800.
[28] Li, N.; Ramil, C. P.; Lim, R. K. V.; Lin, Q. ACS Chem. Biol. 2015, 10, 379.
[29] Li, J.; Lin, S.; Wang, J.; Jia, S.; Yang, M.; Hao, Z.; Zhang, X.; Chen, P. R. J. Am. Chem. Soc. 2013, 135, 7330.
[30] Antos, J. M.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 10256.
[31] Antos, J. M.; McFarland, J. M.; Iavarone, A. T.; Francis, M. B. J. Am. Chem. Soc. 2009, 131, 6301.
[32] Ball, Z. T. Acc. Chem. Res. 2013, 46, 560.
[33] Lin, Y. A.; Chalker, J. M.; Floyd, N.; Bernardes, G. J. L.; Davis, B. G. J. Am. Chem. Soc. 2008, 130, 9642.
[34] Lin, Y. A.; Boutureira, O.; Lercher, L.; Bhushan, B.; Paton, R. S.; Davis, B. G. J. Am. Chem. Soc. 2013, 135, 12156.
[35] (a) Song, W.; Wang, Y.; Qu, J.; Madden, M. M.; Lin, Q. Angew. Chem. Int. Ed. 2008, 47, 2832.
(b) Song, W.; Wang, Y.; Qu, J.; Lin, Q. J. Am. Chem. Soc. 2008, 130, 9654.
(c) Yu, Z.; Pan, Y.; Wang, Z.; Wang, J.; Lin, Q. Angew. Chem., Int. Ed. 2012, 51, 10600.
[36] An, P.; Yu, Z.; Lin, Q. Chem. Commun. 2013, 49, 9920.
[37] Yu, Z.; Lin, Q. J. Am. Chem. Soc. 2014, 136, 4153.
[38] Saxon, E.; Bertozzi, C. R. Science 2000, 287, 2007.
[39] Lemieux, G. A.; de Graffenried, C. L.; Bertozzi, C. R. J. Am. Chem. Soc. 2003, 125, 4708.
[40] (a) Soellner, M. B.; Nilsson, B. L.; Raines, R. T. J. Am. Chem. Soc. 2006, 128, 8820.
(b) Tam, A.; Raines, R. T. Bioorg. Med. Chem. 2009, 17, 1055.
(c) Fang, G.; Wang, C.; Shi, J.; Guo, Q. Acta Chim. Sinica 2009, 67, 2335.(方葛敏, 王晨, 石景, 郭庆祥, 化学学报, 2009, 67, 2335.)
[41] Agard, N. J.; Prescher, J. A.; Bertozzi, C. R. J. Am. Chem. Soc. 2004, 126, 15046.
[42] Codelli, J. A.; Baskin, J. M.; Agard, N. J.; Bertozzi, C. R. J. Am. Chem. Soc. 2008, 130, 11486.
[43] Ning, X.; Guo, J.; Wolfert, M. A.; Boons, G.-J. Angew. Chem., Int. Ed. 2008, 47, 2253.
[44] (a) Sletten, E. M.; Bertozzi, C. R. Org. Lett. 2008, 10, 3097.
(b) Debets, M. F.; van Berkel, S. S.; Schoffelen, S.; Rutjes, F. P. J. T.; van Hest, J. C. M.; van Delft, F. L. Chem. Commun. 2010, 46, 97.
(c) Dommerholt, J.; Schmidt, S.; Temming, R.; Hendriks, L. J. A.; Rutjes, F. P. J. T.; van Hest, J. C. M.; Lefeber, D. J.; Friedl, P.; van Delft, F. L. Angew. Chem., Int. Ed. 2010, 49, 9422.
(d) Jewett, J. C.; Sletten, E. M.; Bertozzi, C. R. J. Am. Chem. Soc. 2010, 132, 3688.
(e) Sletten, E. M.; Nakamura, H.; Jewett, J. C.; Bertozzi, C. R. J. Am. Chem. Soc. 2010, 132, 11799.
(f) de Almeida, G.; Sletten, E. M.; Nakamura, H.; Palaniappan, K. K.; Bertozzi, C. R. Angew. Chem., Int. Ed. 2012, 51, 2443.
[45] Ning, X.; Temming, R. P.; Dommerholt, J.; Guo, J.; Ania, D. B.; Debets, M. F.; Wolfert, M. A.; Boons, G.-J.; van Delft, F. L. Angew. Chem., Int. Ed. 2010, 49, 3065.
[46] McKay, C. S.; Blake, J. A.; Cheng, J.; Danielson, D. C.; Pezacki, J. P. Chem. Commun. 2011, 47, 10040.
[47] Blackman, M. L.; Royzen, M.; Fox, J. M. J. Am. Chem. Soc. 2008, 130, 13518.
[48] Devaraj, N. K.; Weissleder, R.; Hilderbrand, S. A. Bioconjugate Chem. 2008, 19, 2297.
[49] Lang, K.; Davis, L.; Torres-Kolbus, J.; Chou, C.; Deiters, A.; Chin, J. W. Nat. Chem. 2012, 4, 298.
[50] Seitchik, J. L.; Peeler, J. C.; Taylor, M. T.; Blackman, M. L.; Rhoads, T. W.; Cooley, R. B.; Refakis, C.; Fox, J. M.; Mehl, R. A. J. Am. Chem. Soc. 2012, 134, 2898.
[51] Plass, T.; Milles, S.; Koehler, C.; Szymański, J.; Mueller, R.; Wießler, M.; Schultz, C.; Lemke, E. A. Angew. Chem., Int. Ed. 2012, 51, 4166.
[52] Lang, K.; Davis, L.; Wallace, S.; Mahesh, M.; Cox, D. J.; Blackman, M. L.; Fox, J. M.; Chin, J. W. J. Am. Chem. Soc. 2012, 134, 10317.
[53] Xiong, D.-C.; Zhu, J.; Han, M.-J.; Luo, H.-X.; Wang, C.; Yu, Y.; Ye, Y.; Tai, G.; Ye, X.-S. Org. Biomol. Chem. 2015, 13, 3911.
[54] Patterson, D. M.; Nazarova, L. A.; Xie, B.; Kamber, D. N.; Prescher, J. A. J. Am. Chem. Soc. 2012, 134, 18638.
[55] (a) Sander, E. G.; Jencks, W. P. J. Am. Chem. Soc. 1968, 90, 6154.
(b) Rose, K. J. Am. Chem. Soc. 1994, 116, 30.
(c) Gaertner, H. F.; Rose, K.; Cotton, R.; Timms, D.; Camble, R.; Offord, R. E. Bioconjugate Chem. 1992, 3, 262.
[56] (a) Mahal, L. K.; Yarema, K. J.; Bertozzi, C. R. Science 1997, 276, 1125.
(b) Hang, H. C.; Bertozzi, C. R. J. Am. Chem. Soc. 2001, 123, 1242.
[57] (a) Dirksen, A.; Hackeng, T. M.; Dawson, P. E. Angew. Chem., Int. Ed. 2006, 45, 7581.
(b) Dirksen, A.; Dirksen, S.; Hackeng, T. M.; Dawson, P. E. J. Am. Chem. Soc. 2006, 128, 15602.
[58] Tian, F.; Lu, Y.; Manibusan, A.; Sellers, A.; Tran, H.; Sun, Y.; Phuong, T.; Barnett, R.; Hehli, B.; Song, F.; DeGuzman, M. J.; Ensari, S.; Pinkstaff, J. K.; Sullivan, L. M.; Biroc, S. L.; Cho, H.; Schultz, P. G.; DiJoseph, J.; Dougher, M.; Ma, D.; Dushin, R.; Leal, M.; Tchistiakova, L.; Feyfant, E.; Gerber, H.-P.; Sapra, P. Proc. Natl. Acad. Sci. USA 2014, 111, 1766.
[59] Kool, E. T.; Crisalli, P.; Chan, K. M. Org. Lett. 2014, 16, 1454.
[60] White, E. H.; McCapra, F.; Field, G. F.; McElroy, W. D. J. Am. Chem. Soc. 1961, 83, 2402.
[61] Ren, H.; Xiao, F.; Zhan, K.; Kim, Y.-P.; Xie, H.; Xia, Z.; Rao, J. Angew. Chem., Int. Ed. 2009, 48, 9658.
[62] Li, X.; Fekner, T.; Ottesen, J. J.; Chan, M. K. Angew. Chem., Int. Ed. 2009, 48, 9184.
[63] Nguyen, D. P.; Elliott, T.; Holt, M.; Muir, T. W.; Chin, J. W. J. Am. Chem. Soc. 2011, 133, 11418.