基于半胱氨酸的蛋白质化学修饰研究进展

doi:10.6023/cjoc202203008

摘要/Abstract

蛋白质是生物体内含量最丰富的生物大分子, 参与了几乎所有生命活动的进程. 蛋白质的化学修饰是研究与调控其理化性质和生物功能的有效方式, 当前大部分蛋白质的化学修饰是基于氨基酸残基侧链上活泼官能团的反应性来实现. 在20种天然氨基酸中, 半胱氨酸由于其巯基具有独特的亲核性、较低的氧化还原电势以及较低的自然丰度等特点, 成为了科学家研究蛋白质化学修饰的首选. 总结了近些年具有代表性的基于半胱氨酸的蛋白质化学修饰的研究进展, 阐述了相关研究的难点, 并对其未来发展方向进行了展望.

关键词: 多肽修饰, 蛋白质化学修饰, 半胱氨酸

Proteins are the most abundant biomolecules in nature and are involved almost in all living processes. Chemical modification of proteins is an efficient strategy to mediate and study the physical and chemical properties and biological functionalities of proteins. Most protein chemical modifications are based on the bioorthogonal reactivities of the side chain functional groups of certain amino acid residues. Among 20 proteinogenic amino acids, cysteine has become the best choice for chemical protein modification, owning to its relative low abundance in proteins, the unique nucleophilicity and low redox potential of its mercaptan group. The recent advances in chemical protein modification via cysteine are comprehensively reviewed and the challenges and applications for future development are discussed.

Key words: peptide modification, chemical protein modification, cysteine

引用此文

王长流, 赵永丽, 赵军锋. 基于半胱氨酸的蛋白质化学修饰研究进展[J]. 有机化学, 2022, 42(9): 2774-2792.

Changliu Wang, Yongli Zhao, Junfeng Zhao. Recent Advances in Chemical Protein Modification via Cysteine[J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2774-2792.

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图/表 43

图式1. 基于半胱氨酸的蛋白质化学修饰

Scheme 1. Chemical protein modification via cysteine

图式2. 碘代乙酰胺对蛋白半胱氨酸的修饰

Scheme 2. Protein modification using iodoacetamide

图式3. 水溶液中蛋白质上的Suzuki-Miyaura偶联反应

Scheme 3. Protein Suzuki-Miyaura cross-coupling in aqueous media

图式4. 全氟芳香族分子与蛋白质半胱氨酸残基之间的SNAr反应

Scheme 4. SNAr reactions between perfluoroaromatic molecules and cysteine residues in proteins

图式5. 氟苯类试剂对蛋白质半胱氨酸的选择性修饰

Scheme 5. Fluorobenzene reagents for cysteine-selective protein modification

图式6. 半胱氨酸氨乙基化辅助的蛋白质泛素化

Scheme 6. Cysteine-aminoethylation assisted chemical ubiquitination

图式7. 临床获批上市的马来酰亚胺作为连接子的抗体偶联药物

Scheme 7. Clinically-approved ADCs with maleimide as the linker

图式8. 马来酰亚胺-巯基偶联产物的开环以及巯基交换

Scheme 8. Ring opening of maleimide-thiol conjugates and thiol-exchange

图式9. 通过物理拉伸稳定巯基和马来酰亚胺的加成产物

Scheme 9. Maleimide-thiol adducts stabilized through stretching

图式10. 羰基丙烯酸酯类试剂对多肽和蛋白质Cys的不可逆修饰

Scheme 10. Irreversible modification of polypeptide and protein Cys using carbonylacrylic reagents

图式11. 2-叠氮丙烯酸酯作为多肽和蛋白质Cys修饰的双功能试剂

Scheme 11. 2-Azoacrylates as bifunctional reagents for peptide and protein Cys modification

图式12. 5-亚甲基吡咯酮作为高选择性且可无痕脱除的蛋白质巯基修饰试剂

Scheme 12. 5-Methylene pyrrolidone as a highly selective and traceless protein Cys modification reagent

图式13. 3-溴-5-亚甲基吡咯酮作为选择性蛋白质Cys多官能团化和二硫桥环化的修饰试剂

Scheme 13. 3-Bromo-5-methylene pyrrolones as cysteine-specific protein multi-functionalization and disulfide rebridging

图式14. 4-取代环戊烯酮作为高活性且可以无痕脱除的蛋白质巯基修饰试剂

Scheme 14. 4-Substituted cyclopentenone as a highly active and traceless protein thiol modification reagent

图式15. N-甲基-N-苯基乙烯基磺酰胺选择性地和巯基生物偶联

Scheme 15. N-Methyl-N-phenylvinylsulfonamides for cysteine-selective conjugation

图式16. 二硝基吡唑作为双功能生物偶联试剂在蛋白质修饰和多肽环化中的应用

Scheme 16. Dinitroimidazoles as bifunctional bioconjugation reagents for protein modification and peptide macrocyclization

图式17. 含炔基高价碘试剂对多肽和蛋白质的功能化

Scheme 17. Alkynye containing hypervalent iodine-mediated peptide and protein functionalization

图式18. 位点选择性的半胱氨酸-环辛炔衍偶联

Scheme 18. Site-selective cysteine-cyclooctyne conjugation

图式19. 5-(炔基)二苯并噻吩硫鎓-三氟甲磺酸盐通过亲电炔基化反应对蛋白质巯基的修饰

Scheme 19. Protein cysteine modification by electrophilic alkynylation using 5-(alkynyl)dibenzothiophenium triflates

图式20. 缺电子炔烃作为可脱除的蛋白质巯基修饰试剂

Scheme 20. Electron-deficient alkynes as cleavable reagents for protein cysteine modification

图式21. 季铵盐化的烯烃和炔烃吡啶化合物对多肽和蛋白质Cys的修饰

Scheme 21. Quaternization of vinyl/alkynyl pyridine for the modification of cysteine-containing peptides

图式22. 乙烯基膦酸盐和二乙炔基膦酸盐在多肽和蛋白质功能化方面的应用

Scheme 22. Application of ethynyl phosphonamidate and diethynyl phosphinates for peptide and protein functionalization

图式23. 联烯酰胺作为巯基的选择性修饰试剂

Scheme 23. Allenamides as selective reagents for peptide and protein cysteine modification

图式24. 炔酰胺作为高选择性的蛋白质Cys化学修饰试剂

Scheme 24. Ynamide as high cysteine-selective modification reagent

图式25. 铑催化的重氮化合物对半胱氨酸的修饰

Scheme 25. Rhodium-catalyzed cysteine modification with diazo reagents

图式26. 金属钯试剂对多肽和蛋白质半胱氨酸的芳基化修饰

Scheme 26. Palladium reagents for peptide and protein cysteine modification

图式27. 有机金试剂对多肽和蛋白质半胱氨酸的芳基化

Scheme 27. Arylation of peptides and protein cysteine with organometallic gold reagents

图式28. 位点选择性的蛋白质乙酰化

Scheme 28. Site-selective protein acetylation

图式29. 多肽和蛋白质半胱氨酸的选择性和可逆光化学衍生化

Scheme 29. Selective and reversible photochemical derivatization of cysteine residues in peptides and proteins

图式30. 巯基-炔反应在合成订书肽上的应用

Scheme 30. Application of thio-yne reaction in stapled peptide synthesis

图式31. 可见光介导的光催化剂催化的硫-烯反应

Scheme 31. Visible light mediated thiol-ene reactions catalyzed by organic photoredox catalysis

图式32. 镍-钌共催化的半胱氨酸芳基化

Scheme 32. Cysteine arylation using dual nickel-ruthenium catalysis

图式33. 蛋白质层面上配体导向的半胱氨酸修饰

Scheme 33. Ligand directed modification of cysteine at the protein level

图式34. 形成二硫化物的常用方法

Scheme 34. Common methods for disulfide formation

图式35. 2-FPBA作为选择性的N端半胱氨酸修饰试剂

Scheme 35. 2-FPBA as selective N-terminal cysteine modification reagent

图式36. TAMM作为N-端半胱氨酸修饰试剂

Scheme 36. TAMM as N-terminal Cys modification reagent

图式37. BAA作为N-端半胱氨酸修饰试剂

Scheme 37. BAA as N-terminal Cys modification reagent

图式38. 铜离子介导的基于硒代半胱氨酸的多肽和蛋白质化学修饰

Scheme 38. Copper-mediated modification of selenocysteines in peptides and proteins

图式39. 多肽的18F三氟甲基化

Scheme 39. 18F-Trifluoromethylation of peptides

图式40. 异噁唑啉对多肽和蛋白质半胱氨酸的选择性化学修饰

Scheme 40. Cys-selective modification of peptides and proteins using isoxazoliniums

图式41. 不涉及酶的多肽和蛋白质的立体选择性的硫-糖基化

Scheme 41. Nonenzymatic stereoselective S-glycosylation of peptides and proteins

图式42. 甲磺酰基苯基噁二唑类试剂对巯基的化学选择性标记

Scheme 42. Chemoselective labeling of thiols with methylsulfonylphenyloxadiazole reagents

图式43. 硒-硫连接的糖肽和糖蛋白的合成

Scheme 43. Synthesis of selenenylsulfide-linked homogeneous glycopeptides and glycoproteins

参考文献 86

[1]	Walsh, C. T.; Garneau-Tsodikova, S.; Gatto, G. J. Jr. Angew. Chem. Int. Ed. 2005, 44, 7342. doi: 10.1002/anie.200501023
[2]	Chatterjee, S.; Moon, S.; Hentschel, F.; Gilmore, K.; Seeberger, P. H. J. Am. Chem. Soc. 2018, 140, 11942. doi: 10.1021/jacs.8b04525 pmid: 30125122
[3]	Bucci, M. Nat. Chem. Biol. 2018, 14, 525.
[4]	Diallo, I.; Seve, M.; Cunin, V.; Minassian, F.; Poisson, J.-F.; Michelland, S.; Bourgoin-Voillard, S. Expert Rev. Proteomics 2019, 16, 139. doi: 10.1080/14789450.2019.1559061
[5]	Doerr, A. Nat. Med. 2018, 15, 651.
[6]	Prescher, J. A.; Bertozzi, C. R. Nat. Chem. Biol. 2005, 1, 13. doi: 10.1038/nchembio0605-13
[7]	Kennedy, P. J.; Oliveira, C.; Granja, P. L. Pharmacol. Ther. 2017, 177, 129. doi: 10.1016/j.pharmthera.2017.03.004
[8]	Lawrence, P. B.; Price, J. L. Curr. Opin. Chem. Biol. 2016, 34, 88. doi: S1367-5931(16)30103-X pmid: 27580482
[9]	Schlatzer, T.; Kriegesmann, J.; Schroder, H.; Trobe, M.; Lembacher-Fadum, C.; Santner, S.; Kravchuk, A. V.; Becker, C. F. W.; Breinbauer, R. J. Am. Chem. Soc. 2019, 141, 14931. doi: 10.1021/jacs.9b08279 pmid: 31469558
[10]	(a) Yang, M.-Y.; Chen, P. Acta Chim. Sinica 2015, 73, 783. (in Chinese) pmid: 31657212
	(杨麦云, 陈鹏, 化学学报, 2015, 73, 783.) doi: 10.6023/A15030214 pmid: 31657212
	(b) Zheng, Y.; Zhai, L.; Zhao, Y.; Wu, C. J. Am. Chem. Soc. 2015, 137, 15094. doi: 10.1021/jacs.5b10779 pmid: 31657212
	(c) Luo, Q.; Tao, Y.; Sheng, W.; Lu, J.; Wang, H. Nat. Commun. 2019, 10, 142. doi: 10.1038/s41467-018-08010-2 pmid: 31657212
	(d) Zhang, Y.; Zhang, Q.; Wong, C. T. T.; Li, X. J. Am. Chem. Soc. 2019, 141, 12274. doi: 10.1021/jacs.9b03623 pmid: 31657212
	(e) Zhang, Q.; Zhang, Y.; Liu, H.; Chow, H. Y.; Tian, R.; Eva Fung, Y. M.; Li, X. Biochemistry 2020, 59, 175. doi: 10.1021/acs.biochem.9b00787 pmid: 31657212
	(f) Zhao, K.; Lim, Y.-J.; Liu, Z.; Long, H.; Sun, Y.; Hu, J.-J.; Zhao, C.; Tao, Y.; Zhang, X.; Li, D.; Li, Y.-M.; Liu, C. Proc. Natl. Acad. Sci. 2020, 117, 20305. doi: 10.1073/pnas.1922741117 pmid: 31657212
	(g) Wang, S.; Zhou, Q.; Chen, X.; Luo, R.-H.; Li, Y.; Liu, X.; Yang, L.-M.; Zheng, Y.-T.; Wang, P. Nat. Commun. 2021, 12, 2257. doi: 10.1038/s41467-021-22654-7 pmid: 31657212
[11]	Chambers, I.; Frampton, J.; Goldfarb, P.; Affara, N.; Mcbain, W.; Harrison, P. R. EMBO J. 1986, 5, 1221. doi: 10.1002/j.1460-2075.1986.tb04350.x pmid: 3015592
[12]	Giles, N. M.; Watts, A. B.; Giles, G. I.; Fry, F. H.; Littlechild, J. A.; Jacob, C. Chem. Biol. 2003, 10, 677. doi: 10.1016/S1074-5521(03)00174-1
[13]	Marino, S. M.; Gladyshev, V. N. J. Mol. Biol. 2010, 404, 902. doi: 10.1016/j.jmb.2010.09.027
[14]	(a) Chalker, J. M.; Bernardes, G. J.; Lin, Y. A.; Davis, B. G. Chem.- Asian J. 2009, 4, 630. doi: 10.1002/asia.200800427 pmid: 26789551
	(b) Gunnoo, S. B.; Madder, A. ChemBioChem 2016, 17, 529. doi: 10.1002/cbic.201500667 pmid: 26789551
	(c) Ochtrop, P.; Hackenberger, C. P. R. Curr. Opin. Chem. Biol. 2020, 58, 28. doi: 10.1016/j.cbpa.2020.04.017 pmid: 26789551
[15]	Goddard, D. R., Michaelis, L. J. Biol. Chem. 1935, 112, 361. doi: 10.1016/S0021-9258(18)74993-4
[16]	Nielsen, M. L.; Vermeulen, M.; Bonaldi, T.; Cox, J.; Moroder, L.; Mann, M. Nat. Med. 2008, 5, 459. doi: 10.1038/7458
[17]	Zhang, C.; Vinogradova, E. V.; Spokoyny, A. M.; Buchwald, S. L.; Pentelute, B. L. Angew. Chem., Int. Ed. 2019, 58, 4810. doi: 10.1002/anie.201806009 pmid: 30399206
[18]	Chalker, J. M.; Wood, C. S. C.; Davis, B. G. J. Am. Chem. Soc. 2009, 131, 16346. doi: 10.1021/ja907150m pmid: 19852502
[19]	Spokoyny, A. M.; Zou, Y.; Ling, J. J.; Yu, H.; Lin, Y. S.; Pentelute, B. L. J. Am. Chem. Soc. 2013, 135, 5946. doi: 10.1021/ja400119t
[20]	Zhang, C.; Spokoyny, A. M.; Zou, Y.; Simon, M. D.; Pentelute, B. L. Angew. Chem., Int. Ed. 2013, 52, 14001. doi: 10.1002/anie.201306430 pmid: 24222025
[21]	Zhang, C.; Welborn, M.; Zhu, T.; Yang, N. J.; Santos, M. S.; Van Voorhis, T.; Pentelute, B. L. Nat. Chem. 2015, 8, 120. doi: 10.1038/nchem.2413
[22]	Embaby, A. M.; Schoffelen, S.; Kofoed, C.; Meldal, M.; Diness, F. Angew. Chem., Int. Ed. 2018, 57, 8022. doi: 10.1002/anie.201712589 pmid: 29469231
[23]	Bell, O.; Tiwari, V. K.; Thoma, N. H.; Schubeler, D. Nat. Rev. Genet. 2011, 12, 554.
[24]	Chu, G.-C.; Pan, M.; Li, J.; Liu, S.; Zuo, C.; Tong, Z.-B.; Bai, J.-S.; Gong, Q.; Ai, H.; Fan, J.; Meng, X.; Huang, Y.-C.; Shi, J.; Deng, H.; Tian, C.; Li, Y.-M.; Liu, L. J. Am. Chem. Soc. 2019, 141, 3654. doi: 10.1021/jacs.8b13213
[25]	Diamantis, N.; Banerji, U. Br. J. Cancer 2016, 114, 362. doi: 10.1038/bjc.2015.435
[26]	Walsh, S. J.; Bargh, J. D.; Dannheim, F. M.; Hanby, A. R.; Seki, H.; Counsell, A. J.; Ou, X.; Fowler, E.; Ashman, N.; Takada, Y.; Isidro-Llobet, A.; Parker, J. S.; Carroll, J. S.; Spring, D. R. Chem. Soc. Rev. 2021, 50, 1305. doi: 10.1039/D0CS00310G
[27]	(a) Tedaldi, L. M.; Smith, M. E.; Nathani, R. I.; Baker, J. R. Chem. Commun. 2009, 6583. pmid: 34760149
	(b) Kang, M. S.; Kong, T. W. S.; Khoo, J. Y. X.; Loh, T.-P. Chem. Sci. 2021, 12, 13613. doi: 10.1039/d1sc02973h pmid: 34760149
[28]	Christie, R. J.; Fleming, R.; Bezabeh, B.; Woods, R.; Mao, S.; Harper, J.; Joseph, A.; Wang, Q.; Xu, Z.-Q.; Wu, H.; Gao, C.; Dimasi, N. J. Controlled Release 2015, 220, 660. doi: 10.1016/j.jconrel.2015.09.032
[29]	Lyon, R. P.; Setter, J. R.; Bovee, T. D.; Doronina, S. O.; Hunter, J. H.; Anderson, M. E.; Balasubramanian, C. L.; Duniho, S. M.; Leiske, C. I.; Li, F.; Senter, P. D. Nat. Biotechnol. 2014, 32, 1059. doi: 10.1038/nbt.2968
[30]	Ravasco, J.; Faustino, H.; Trindade, A.; Gois, P. M. P. Chem.-Eur. J. 2019, 25, 43. doi: 10.1002/chem.201803174 pmid: 30095185
[31]	Huang, W.; Wu, X.; Gao, X.; Yu, Y.; Lei, H.; Zhu, Z.; Shi, Y.; Chen, Y.; Qin, M.; Wang, W.; Cao, Y. Nat. Chem. 2019, 11, 310. doi: 10.1038/s41557-018-0209-2
[32]	Bernardim, B.; Cal, P. M.; Matos, M. J.; Oliveira, B. L.; Martinez-Saez, N.; Albuquerque, I. S.; Perkins, E.; Corzana, F.; Burtoloso, A. C.; Jimenez-Oses, G.; Bernardes, G. J. Nat. Commun. 2016, 7, 13128. doi: 10.1038/ncomms13128 pmid: 27782215
[33]	Ariyasu, S.; Hayashi, H.; Xing, B.; Chiba, S. Bioconjugate Chem. 2017, 28, 897. doi: 10.1021/acs.bioconjchem.7b00024 pmid: 28212596
[34]	Zhang, Y.; Zhou, X.; Xie, Y.; Greenberg, M. M.; Xi, Z.; Zhou, C. J. Am. Chem. Soc. 2017, 139, 6146. doi: 10.1021/jacs.7b00670
[35]	Zhang, Y.; Zang, C.; An, G.; Shang, M.; Cui, Z.; Chen, G.; Xi, Z.; Zhou, C. Nat. Commun. 2020, 11, 1015. doi: 10.1038/s41467-020-14757-4
[36]	Yu, J.; Yang, X.; Sun, Y.; Yin, Z. Angew. Chem., Int. Ed. 2018, 57, 11598. doi: 10.1002/anie.201804801
[37]	Huang, R.; Li, Z.; Sheng, Y.; Yu, J.; Wu, Y.; Zhan, Y.; Chen, H.; Jiang, B. Org. Lett. 2018, 20, 6526. doi: 10.1021/acs.orglett.8b02849 pmid: 30284842
[38]	Hoogenboom, R. Angew. Chem., Int. Ed. 2010, 49, 3415. doi: 10.1002/anie.201000401 pmid: 20394091
[39]	(a) Frei, R.; Waser, J. J. Am. Chem. Soc. 2013, 135, 9620. doi: 10.1021/ja4044196
	(b) Frei, R.; Wodrich, M. D.; Hari, D. P.; Borin, P.-A.; Chauvier, C.; Waser, J. J. Am. Chem. Soc. 2014, 136, 16563. doi: 10.1021/ja5083014
[40]	Abegg, D.; Frei, R.; Cerato, L.; Prasad Hari, D.; Wang, C.; Waser, J.; Adibekian, A. Angew. Chem., Int. Ed. 2015, 54, 10852. doi: 10.1002/anie.201505641
[41]	Tessier, R.; Ceballos, J.; Guidotti, N.; Simonet-Davin, R.; Fierz, B.; Waser, J. Chem 2019, 5, 2243. doi: 10.1016/j.chempr.2019.06.002
[42]	Tessier, R.; Nandi, R. K.; Dwyer, B. G.; Abegg, D.; Sornay, C.; Ceballos, J.; Erb, S.; Cianferani, S.; Wagner, A.; Chaubet, G.; Adibekian, A.; Waser, J. Angew. Chem., Int. Ed. 2020, 59, 10961. doi: 10.1002/anie.202002626 pmid: 32233093
[43]	(a) Ceballos, J.; Grinhagena, E.; Sangouard, G.; Heinis, C.; Waser, J. Angew. Chem., Int. Ed. 2021, 60, 9022. doi: 10.1002/anie.202014511 pmid: 33450121
	(b) Ceballos, J.; Grinhagena, E.; Sangouard, G.; Heinis, C.; Waser, J. Angew. Chem., Int. Ed. 2021, 60, 9022. doi: 10.1002/anie.202014511 pmid: 33450121
	(c) Allouche, E. M. D.; Grinhagena, E.; Waser, J. Angew. Chem., Int. Ed. 2021, 60, 2. doi: 10.1002/anie.202014556 pmid: 33450121
[44]	Zhang, C.; Dai, P.; Vinogradov, A. A.; Gates, Z. P.; Pentelute, B. L. Angew. Chem., Int. Ed. 2018, 57, 6459. doi: 10.1002/anie.201800860 pmid: 29575377
[45]	Laserna, V.; Istrate, A.; Kafuta, K.; Hakala, T. A.; Knowles, T. P. J.; Alcarazo, M.; Bernardes, G. J. L. Bioconjugate Chem. 2021, 32, 1570. doi: 10.1021/acs.bioconjchem.1c00317 pmid: 34232618
[46]	Truce, W. E.; Tichenor, G. J. W. J. Org. Chem. 1972, 37, 2391. doi: 10.1021/jo00980a007
[47]	Arjona, O.; Iradier, F.; Medel, R.; Plumet, J. J. Org. Chem. 1999, 64, 6090. doi: 10.1021/jo990308c
[48]	Arjona, O.; Medel, R. o.; Rojas, J.; Costa, A. M.; Vilarrasa, J. Tetrahedron Lett. 2003, 44, 6369. doi: 10.1016/S0040-4039(03)01614-9
[49]	Shiu, H. Y.; Chan, T. C.; Ho, C. M.; Liu, Y.; Wong, M. K.; Che, C. M. Chem.-Eur. J. 2009, 15, 3839. doi: 10.1002/chem.200800669
[50]	Matos, M. J.; Navo, C. D.; Hakala, T.; Ferhati, X.; Guerreiro, A.; Hartmann, D.; Bernardim, B.; Saar, K. L.; Companon, I.; Corzana, F.; Knowles, T. P. J.; Jimenez-Oses, G.; Bernardes, G. J. L. Angew. Chem., Int. Ed. 2019, 58, 6640. doi: 10.1002/anie.201901405
[51]	Vallee, M. R.; Majkut, P.; Wilkening, I.; Weise, C.; Muller, G.; Hackenberger, C. P. Org. Lett. 2011, 13, 5440. doi: 10.1021/ol2020175
[52]	(a) Kasper, M. A.; Glanz, M.; Stengl, A.; Penkert, M.; Klenk, S.; Sauer, T.; Schumacher, D.; Helma, J.; Krause, E.; Cardoso, M. C.; Leonhardt, H.; Hackenberger, C. P. R. Angew. Chem., Int. Ed. 2019, 58, 11625. doi: 10.1002/anie.201814715
	(b) Park, Y.; Baumann, A. L.; Moon, H.; Byrne, S.; Kasper, M. A.; Hwang, S.; Sun, H.; Baik, M. H.; Hackenberger, C. P. R. Chem. Sci. 2021, 12, 8141. doi: 10.1039/D1SC01730F
[53]	Kasper, M.-A.; Glanz, M.; Oder, A.; Schmieder, P.; von Kries, J. P.; Hackenberger, C. P. R. Chem. Sci. 2019, 10, 6322. doi: 10.1039/C9SC01345H
[54]	Kasper, M. A.; Stengl, A.; Ochtrop, P.; Gerlach, M.; Stoschek, T.; Schumacher, D.; Helma, J.; Penkert, M.; Krause, E.; Leonhardt, H.; Hackenberger, C. P. R. Angew. Chem., Int. Ed. 2019, 58, 11631. doi: 10.1002/anie.201904193
[55]	Stieger, C. E.; Franz, L.; Korlin, F.; Hackenberger, C. P. R. Angew. Chem., Int. Ed. 2021, 60, 1.
[56]	Abbas, A.; Xing, B.; Loh, T.-P. Angew. Chem., Int. Ed. 2014, 53, 7491. doi: 10.1002/anie.201403121 pmid: 24889524
[57]	(a) Peng, Z.; Zhang, Z.; Tu, Y.; Zeng, X.; Zhao, J. Org. Lett. 2018, 20, 5688. doi: 10.1021/acs.orglett.8b02409
	(b) Peng, Z.; Zhang, Z.; Zeng, X.; Tu, Y.; Zhao, J. Adv. Synth. Catal. 2019, 361, 4489. doi: 10.1002/adsc.201900734
[58]	Wang, C.; Zhao, Z.; Ghadir, R.; Li, Y.; Zhao, Y.; Metanis, N.; Zhao, J. ChemRxiv 2021, doi: 10.26434/chemrxiv-2021-9gxpp. doi: 10.26434/chemrxiv-2021-9gxpp
[59]	(a) Ashenhurst, J. A. Chem. Soc. Rev. 2010, 39, 540. doi: 10.1039/b907809f pmid: 20111778
	(b) Yang, Y.; Lan, J.; You, J. Chem. Rev. 2017, 117, 8787. doi: 10.1021/acs.chemrev.6b00567 pmid: 20111778
[60]	(a) Simmons, R. L.; Yu, R. T.; Myers, A. G. J. Am. Chem. Soc. 2011, 133, 15870. doi: 10.1021/ja206339s
	(b) Jbara, M.; Maity, S. K.; Brik, A. Angew. Chem., Int. Ed. 2017, 56, 10644. doi: 10.1002/anie.201702370
	(c) Bai, Z.; Cai, C.; Sheng, W.; Ren, Y.; Wang, H. Angew. Chem., Int. Ed. 2020, 59, 14686. doi: 10.1002/anie.202007226
	(d) Zhang, X.; Lu, G.; Sun, M.; Mahankali, M.; Ma, Y.; Zhang, M.; Hua, W.; Hu, Y.; Wang, Q.; Chen, J.; He, G.; Qi, X.; Shen, W.; Liu, P.; Chen, G. Nat. Chem. 2018, 10, 540. doi: 10.1038/s41557-018-0006-y
[61]	Kundu, R.; Ball, Z. T. Chem. Commun. 2013, 49, 4166. doi: 10.1039/C2CC37323H
[62]	Vinogradova, E. V.; Zhang, C.; Spokoyny, A. M.; Pentelute, B. L.; Buchwald, S. L. Nature 2015, 526, 687. doi: 10.1038/nature15739
[63]	Rojas, A. J.; Zhang, C.; Vinogradova, E. V.; Buchwald, N. H.; Reilly, J.; Pentelute, B. L.; Buchwald, S. L. Chem. Sci. 2017, 8, 4257. doi: 10.1039/C6SC05454D
[64]	Rojas, A. J.; Pentelute, B. L.; Buchwald, S. L. Org. Lett. 2017, 19, 4263. doi: 10.1021/acs.orglett.7b01911
[65]	Jbara, M.; Pomplun, S.; Schissel, C. K.; Hawken, S. W.; Boija, A.; Klein, I.; Rodriguez, J.; Buchwald, S. L.; Pentelute, B. L. J. Am. Chem. Soc. 2021, 143, 11788. doi: 10.1021/jacs.1c05666
[66]	Messina, M. S.; Stauber, J. M.; Waddington, M. A.; Rheingold, A. L.; Maynard, H. D.; Spokoyny, A. M., J. Am. Chem. Soc. 2018, 140, 7065. doi: 10.1021/jacs.8b04115 pmid: 29790740
[67]	Kulkarni, S. S.; Sayers, J.; Premdjee, B.; Payne, R. J. Nat. Rev. Chem. 2018, 2, 0122. doi: 10.1038/s41570-018-0122
[68]	Li, F.; Allahverdi, A.; Yang, R.; Lua, G. B. J.; Zhang, X.; Cao, Y.; Korolev, N.; Nordenskiöld, L.; Liu, C.-F. Angew. Chem., Int. Ed. 2011, 50, 9611. doi: 10.1002/anie.201103754
[69]	Arumugam, S.; Guo, J.; Mbua, N. E.; Friscourt, F.; Lin, N.; Nekongo, E.; Boons, G.-J.; Popik, V. V. Chem. Sci. 2014, 5, 1591. doi: 10.1039/C3SC51691A
[70]	(a) Hu, K.; Geng, H.; Zhang, Q.; Liu, Q.; Xie, M.; Sun, C.; Li, W.; Lin, H.; Jiang, F.; Wang, T.; Wu, Y.-D.; Li, Z. Angew. Chem., Int. Ed. 2016, 55, 8013. doi: 10.1002/anie.201602806
	(b) Tian, Y.; Li, J.; Zhao, H.; Zeng, X.; Wang, D.; Liu, Q.; Niu, X.; Huang, X.; Xu, N.; Li, Z. Chem. Sci. 2016, 7, 3325. doi: 10.1039/C6SC00106H
[71]	Zhao, G.; Kaur, S.; Wang, T. Org. Lett. 2017, 19, 3291. doi: 10.1021/acs.orglett.7b01441
[72]	Vara, B. A.; Li, X.; Berritt, S.; Walters, C. R.; Petersson, E. J.; Molander, G. A. Chem. Sci. 2018, 9, 336. doi: 10.1039/C7SC04292B
[73]	Beard, H. A.; Hauser, J. R.; Walko, M.; George, R. M.; Wilson, A. J.; Bon, R. S. Commun. Chem. 2019, 2, 133. doi: 10.1038/s42004-019-0235-z
[74]	Bulaj, G. Biotechnol. Adv. 2005, 23, 87. doi: 10.1016/j.biotechadv.2004.09.002
[75]	(a) Chalker, J. M.; Bernardes, G. J. L.; Davis, B. G. Acc. Chem. Res. 2011, 44, 730. doi: 10.1021/ar200056q pmid: 22173886
	(b) van Kasteren, S. Biochem. Soc. Trans. 2012, 40, 929. doi: 10.1042/BST20120144 pmid: 22173886
	(c) Bernardes, G. J. L.; Casi, G.; Trissel, S.; Hartmann, I.; Schwager, K.; Scheuermann, J.; Neri, D. Angew. Chem., Int. Ed. 2012, 51, 941. doi: 10.1002/anie.201106527 pmid: 22173886
	(d) List, T.; Casi, G.; Neri, D. Mol. Cancer Ther. 2014, 13, 2641. doi: 10.1158/1535-7163.MCT-14-0599 pmid: 22173886
[76]	Dawson, P. E.; Muir, T. W.; Clarklewis, I.; Kent, S. B. H. Science 1994, 266, 776. pmid: 7973629
[77]	Faustino, H.; Silva, M. J. S. A.; Veiros, L. F.; Bernardes, G. J. L.; Gois, P. M. P. Chem. Sci. 2016, 7, 6280. doi: 10.1039/c6sc90045c pmid: 30124674
[78]	Zheng, X.; Li, Z.; Gao, W.; Meng, X.; Li, X.; Luk, L. Y. P.; Zhao, Y.; Tsai, Y.-H.; Wu, C. J. Am. Chem. Soc. 2020, 142, 5097. doi: 10.1021/jacs.9b11875
[79]	Wu, Y.; Li, C.; Fan, S.; Zhao, Y.; Wu, C. Bioconjugate Chem. 2021, 32, 2065. doi: 10.1021/acs.bioconjchem.1c00378
[80]	King, T. A.; Mandrup Kandemir, J.; Walsh, S. J.; Spring, D. R., Chem. Soc. Rev. 2021, 50, 39. doi: 10.1039/D0CS00344A
[81]	Zhao, Z.; Shimon, D.; Metanis, N. J. Am. Chem. Soc. 2021, 143, 12817. doi: 10.1021/jacs.1c06101
[82]	Verhoog, S.; Kee, C. W.; Wang, Y.; Khotavivattana, T.; Wilson, T. C.; Kersemans, V.; Smart, S.; Tredwell, M.; Davis, B. G.; Gouverneur, V. J. Am. Chem. Soc. 2018, 140, 1572. doi: 10.1021/jacs.7b10227 pmid: 29301394
[83]	Deng, J.-R.; Chung, S.-F.; Leung, A. S.-L.; Yip, W.-M.; Yang, B.; Choi, M.-C.; Cui, J.-F.; Kung, K. K.-Y.; Zhang, Z.; Lo, K.-W.; Leung, Y.-C.; Wong, M.-K. Commun. Chem. 2019, 2, 93. doi: 10.1038/s42004-019-0193-5
[84]	Wan, L.-Q.; Zhang, X.; Zou, Y.; Shi, R.; Cao, J.-G.; Xu, S.-Y.; Deng, L.-F.; Zhou, L.; Gong, Y.; Shu, X.; Lee, G. Y.; Ren, H.; Dai, L.; Qi, S.; Houk, K. N.; Niu, D. J. Am. Chem. Soc. 2021, 143, 11919. doi: 10.1021/jacs.1c05156
[85]	Toda, N.; Asano, S.; Barbas III, C. F. Angew. Chem., Int. Ed. 2013, 52, 12592. doi: 10.1002/anie.201306241
[86]	Boutureira, O.; Bernardes, G. J. L.; Fernández-González, M.; Anthony, D. C.; Davis, B. G. Angew. Chem., Int. Ed. 2012, 51, 1432. doi: 10.1002/anie.201106658 pmid: 22213253