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Homogeneous Glycoprotein Synthesis Utilizing Bifunctional Glycosyl α-Amino Thioacid

野村, 幸汰 大阪大学

2022.03.24

概要

Glycosylation is a major modification of secreted and cell surface proteins, however the resultant glycans show a considerable heterogeneity in their structures. To understand the biological functions arising from each glycoform, the preparation of homogeneous glycoproteins is essential for extensive biological experiments. To establish a more robust and rapid synthetic route of homogeneous glycoproteins, several key reactions based on α-amino thioacids have been studied. Extensive studies found that diacyl disulfide coupling (DDC) between a glycosyl asparagine thioacid B and a peptide thioacid A yielded a glycopeptide thioacid C (Figure 1).

This efficient coupling reaction enabled me to develop a new glycoprotein synthesis method, chemical glycan insertion strategy, which can insert glycosyl asparagine E between two unprotected peptides D, F (Figure 2). The first coupling is DDC between a peptide thioacid D and a glycosyl asparagine thioacid E. Because the resultant glycopeptide has a thioacid form at its C terminus, the thioacid capture ligation (TCL) can apply to the coupling of glycopeptide thioacid and another peptide F having p-nitropyridylsulfide (Npys) group at its N-terminus to afford the full-length glycoprotein G. Subsequent desulfurization of glycoproteins G can finally yields a natural form of glycoproteins H.

Applying this strategy, bioactive cytokines, interleukin 3 (IL3, 1), CC chemokine ligand 1 (CCL1, 2) and serine protease inhibitor kazal type 13 (SPINK13, 3) having a biantennary sialyloligosaccharide respectively were synthesized within a few steps (Figure 3). Previous glycoprotein synthesis methods required valuable glycosyl asparagine in the early stage and subsequent multiple glycoprotein synthesis routes. However, the developed new concept can generate glycoproteins within a few steps from peptides and glycosyl asparagine thioacids.

In terms of the synthesis of SPINK13 3, DDC and TCL should be performed with the low reactive proline and bulky valine and the synthesis is therefore challenging. The first a glycosyl asparagine thioacid 4 was coupled to an N-terminal peptide prolyl thioacid 5 using DDC to afford the glycopeptide thioacid 6 in 28% yield. Then, the resultant glycopeptide thioacid 6 was coupled with C-terminal peptide having the Npys group at β-mercaptovaline 7 utilizing TCL to give a full-length glycoprotein 8 in 59% yield. After desulfurization and deprotection of Acm protecting groups convergently afforded the linear glycoprotein polypeptide 9 and stepwise dialysis folding conditions gave the desired glycoproteins folded SPINK13 3 (Figure 4).

Furthermore, using homogeneous glycoproteins IL3 1 and SPINK13 3 synthesized by the developed strategy as chemical probes, several in vitro bioassays could be performed. These achievements indicate that our new synthetic strategy of homogeneous glycoproteins can be efficiently applied to not only the synthesis of chemical probes but also the various bioassays for the elucidation of the glycan structure-bioactivity relationship.

参考文献

1. Walsh, G.; Jefferis, R., Post-translational modifications in the context of therapeutic proteins.Nat Biotechnol 2006, 24 (10), 1241-52.

2. Okayama, A.; Miyagi, Y.; Oshita, F.; Ito, H.; Nakayama, H.; Nishi, M.; Kurata, Y.; Kimura, Y.; Ryo, A.; Hirano, H., Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial– Mesenchymal Transition Induced with TGF-β. Journal of Proteome Research 2015, 14 (10), 4127-4136.

3. Nagata, K.; Kawakami, T.; Kurata, Y.; Kimura, Y.; Suzuki, Y.; Nagata, T.; Sakuma, Y.; Miyagi, Y.; Hirano, H., Augmentation of multiple protein kinase activities associated with secondary imatinib resistance in gastrointestinal stromal tumors as revealed by quantitative phosphoproteome analysis. J Proteomics 2015, 115, 132-42.

4. Ishigami, A.; Masutomi, H.; Handa, S.; Nakamura, M.; Nakaya, S.; Uchida, Y.; Saito, Y.; Murayama, S.; Jang, B.; Jeon, Y. C.; Choi, E. K.; Kim, Y. S.; Kasahara, Y.; Maruyama, N.; Toda, T., Mass spectrometric identification of citrullination sites and immunohistochemical detection of citrullinated glial fibrillary acidic protein in Alzheimer's disease brains. J Neurosci Res 2015, 93 (11), 1664-74.

5. Ishigami, A.; Ohsawa, T.; Hiratsuka, M.; Taguchi, H.; Kobayashi, S.; Saito, Y.; Murayama, S.; Asaga, H.; Toda, T.; Kimura, N.; Maruyama, N., Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease. J Neurosci Res 2005, 80 (1), 120-8.

6. Unverzagt, C.; Kajihara, Y., Recent advances in the chemical synthesis of N-linked glycoproteins.Curr Opin Chem Biol 2018, 46, 130-137.

7. Wong, C.-H., Protein Glycosylation: New Challenges and Opportunities. The Journal of Organic Chemistry 2005, 70 (11), 4219-4225.

8. Varki, A., Biological roles of glycans. Glycobiology 2017, 27 (1), 3-49.

9. Wolfert, M. A.; Boons, G. J., Adaptive immune activation: glycosylation does matter. Nat Chem Biol 2013, 9 (12), 776-84.

10. Sinclair, A. M.; Elliott, S., Glycoengineering: the effect of glycosylation on the properties of therapeutic proteins. J Pharm Sci 2005, 94 (8), 1626-35.

11. Rudd, P. M.; Elliott, T.; Cresswell, P.; Wilson, I. A.; Dwek, R. A., Glycosylation and the immune system. Science 2001, 291 (5512), 2370-6.

12. Van den Steen, P.; Rudd, P. M.; Dwek, R. A.; Opdenakker, G., Concepts and principles of O- linked glycosylation. Crit Rev Biochem Mol Biol 1998, 33 (3), 151-208.

13. Lizak, C.; Gerber, S.; Numao, S.; Aebi, M.; Locher, K. P., X-ray structure of a bacterial oligosaccharyltransferase. Nature 2011, 474 (7351), 350-355.

14. Kiuchi, T.; Izumi, M.; Mukogawa, Y.; Shimada, A.; Okamoto, R.; Seko, A.; Sakono, M.; Takeda, Y.; Ito, Y.; Kajihara, Y., Monitoring of Glycoprotein Quality Control System with a Series of Chemically Synthesized Homogeneous Native and Misfolded Glycoproteins. Journal of the American Chemical Society2018, 140 (50), 17499-17507.

15. Helenius, A.; Aebi, M., Roles of N-Linked Glycans in the Endoplasmic Reticulum. Annual Review of Biochemistry 2004, 73 (1), 1019-1049.

16. Shirakawa, A.; Manabe, Y.; Fukase, K., Recent Advances in the Chemical Biology of N-Glycans.Molecules 2021, 26 (4).

17. Dadová, J.; Galan, S. R.; Davis, B. G., Synthesis of modified proteins via functionalization of dehydroalanine. Curr Opin Chem Biol 2018, 46, 71-81.

18. Hirano, K.; Macmillan, D.; Tezuka, K.; Tsuji, T.; Kajihara, Y., Design and synthesis of a homogeneous erythropoietin analogue with two human complex-type sialyloligosaccharides: combined use of chemical and bacterial protein expression methods. Angew Chem Int Ed Engl 2009, 48 (50), 9557-60.

19. Yamamoto, N.; Sakakibara, T.; Kajihara, Y., Convenient synthesis of a glycopeptide analogue having a complex type disialyl-undecasaccharide. Tetrahedron Letters 2004, 45 (16), 3287-3290.

20. Unverzagt, C.; Kajihara, Y., Chemical assembly of N-glycoproteins: a refined toolbox to address a ubiquitous posttranslational modification. Chem Soc Rev 2013, 42 (10), 4408-20.

21. Eller, S.; Schuberth, R.; Gundel, G.; Seifert, J.; Unverzagt, C., Synthesis of pentaantennary N- glycans with bisecting GlcNAc and core fucose. Angew Chem Int Ed Engl 2007, 46 (22), 4173-5.

22. Shivatare, S. S.; Chang, S. H.; Tsai, T. I.; Ren, C. T.; Chuang, H. Y.; Hsu, L.; Lin, C. W.; Li, S. T.; Wu, C. Y.; Wong, C. H., Efficient convergent synthesis of bi-, tri-, and tetra-antennary complex type N- glycans and their HIV-1 antigenicity. J Am Chem Soc 2013, 135 (41), 15382-91.

23. Seko, A.; Koketsu, M.; Nishizono, M.; Enoki, Y.; Ibrahim, H. R.; Juneja, L. R.; Kim, M.; Yamamoto, T., Occurrence of a sialylglycopeptide and free sialylglycans in hen's egg yolk. Biochimica et Biophysica Acta (BBA) - General Subjects 1997, 1335 (1-2), 23-32.

24. Kajihara, Y.; Suzuki, Y.; Yamamoto, N.; Sasaki, K.; Sakakibara, T.; Juneja, L. R., Prompt chemoenzymatic synthesis of diverse complex-type oligosaccharides and its application to the solid-phase synthesis of a glycopeptide with Asn-linked sialyl-undeca- and asialo-nonasaccharides. Chemistry 2004, 10 (4), 971-85.

25. Fukae, K.; Yamamoto, N.; Hatakeyama, Y.; Kajihara, Y., Chemoenzymatic synthesis of diverse asparagine-linked alpha-(2,3)-sialyloligosaccharides. Glycoconj J 2004, 21 (5), 243-50.

26. Maki, Y.; Okamoto, R.; Izumi, M.; Murase, T.; Kajihara, Y., Semisynthesis of Intact Complex- Type Triantennary Oligosaccharides from a Biantennary Oligosaccharide Isolated from a Natural Source by Selective Chemical and Enzymatic Glycosylation. J Am Chem Soc 2016, 138 (10), 3461-8.

27. Maki, Y.; Nomura, K.; Okamoto, R.; Izumi, M.; Mizutani, Y.; Kajihara, Y., Acceleration and Deceleration Factors on the Hydrolysis Reaction of 4,6-O-Benzylidene Acetal Group. The Journal of Organic Chemistry 2020, 85 (24), 15849-15856.

28. Xu, T.; Coward, J. K., 13C- and 15N-labeled peptide substrates as mechanistic probes of oligosaccharyltransferase. Biochemistry 1997, 36 (48), 14683-9.

29. Dempski, R. E.; Imperiali, B., Oligosaccharyl transferase: gatekeeper to the secretory pathway.Current Opinion in Chemical Biology 2002, 6 (6), 844-850.

30. Wang, L. X.; Amin, M. N., Chemical and chemoenzymatic synthesis of glycoproteins for deciphering functions. Chem Biol 2014, 21 (1), 51-66.

31. Chen, M. M.; Glover, K. J.; Imperiali, B., From peptide to protein: comparative analysis of the substrate specificity of N-linked glycosylation in C. jejuni. Biochemistry 2007, 46 (18), 5579-85.

32. Glover, K. J.; Weerapana, E.; Numao, S.; Imperiali, B., Chemoenzymatic synthesis of glycopeptides with PglB, a bacterial oligosaccharyl transferase from Campylobacter jejuni. Chem Biol 2005, 12 (12), 1311-5.

33. Schwarz, F.; Fan, Y. Y.; Schubert, M.; Aebi, M., Cytoplasmic N-glycosyltransferase of Actinobacillus pleuropneumoniae is an inverting enzyme and recognizes the NX(S/T) consensus sequence. J Biol Chem 2011, 286 (40), 35267-74.

34. Lomino, J. V.; Naegeli, A.; Orwenyo, J.; Amin, M. N.; Aebi, M.; Wang, L. X., A two-step enzymatic glycosylation of polypeptides with complex N-glycans. Bioorg Med Chem 2013, 21 (8), 2262- 2270.

35. Wang, L. X.; Lomino, J. V., Emerging technologies for making glycan-defined glycoproteins.ACS Chem Biol 2012, 7 (1), 110-22.

36. Witte, K.; Sears, P.; Martin, R.; Wong, C.-H., Enzymatic Glycoprotein Synthesis: Preparation of Ribonuclease Glycoforms via Enzymatic Glycopeptide Condensation and Glycosylation. Journal of the American Chemical Society 1997, 119 (9), 2114-2118.

37. Fujita, M.; Shoda, S.-i.; Haneda, K.; Inazu, T.; Takegawa, K.; Yamamoto, K., A novel disaccharide substrate having 1,2-oxazoline moiety for detection of transglycosylating activity of endoglycosidases. Biochimica et Biophysica Acta (BBA) - General Subjects 2001, 1528 (1), 9-14.

38. Wang, L. X., Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation. Carbohydr Res 2008, 343 (10-11), 1509-22.

39. Li, B.; Zeng, Y.; Hauser, S.; Song, H.; Wang, L. X., Highly efficient endoglycosidase-catalyzed synthesis of glycopeptides using oligosaccharide oxazolines as donor substrates. J Am Chem Soc 2005, 127 (27), 9692-3.

40. Umekawa, M.; Huang, W.; Li, B.; Fujita, K.; Ashida, H.; Wang, L. X.; Yamamoto, K., Mutants of Mucor hiemalis endo-beta-N-acetylglucosaminidase show enhanced transglycosylation and glycosynthase-like activities. J Biol Chem 2008, 283 (8), 4469-79.

41. Huang, W.; Yang, Q.; Umekawa, M.; Yamamoto, K.; Wang, L. X., Arthrobacter endo-beta-N- acetylglucosaminidase shows transglycosylation activity on complex-type N-glycan oxazolines: one-pot conversion of ribonuclease B to sialylated ribonuclease C. Chembiochem 2010, 11 (10), 1350-5.

42. Ochiai, H.; Huang, W.; Wang, L. X., Expeditious chemoenzymatic synthesis of homogeneous N-glycoproteins carrying defined oligosaccharide ligands. J Am Chem Soc 2008, 130 (41), 13790-803.

43. Noguchi, M.; Tanaka, T.; Gyakushi, H.; Kobayashi, A.; Shoda, S., Efficient synthesis of sugar oxazolines from unprotected N-acetyl-2-amino sugars by using chloroformamidinium reagent in water. J Org Chem 2009, 74 (5), 2210-2.

44. Huang, W.; Groothuys, S.; Heredia, A.; Kuijpers, B. H.; Rutjes, F. P.; van Delft, F. L.; Wang, L. X., Enzymatic glycosylation of triazole-linked GlcNAc/Glc-peptides: synthesis, stability and anti-HIV activity of triazole-linked HIV-1 gp41 glycopeptide C34 analogues. Chembiochem 2009, 10 (7), 1234-42.

45. Huang, W.; Giddens, J.; Fan, S. Q.; Toonstra, C.; Wang, L. X., Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions. J Am Chem Soc 2012, 134 (29), 12308-18.

46. Fan, S. Q.; Huang, W.; Wang, L. X., Remarkable transglycosylation activity of glycosynthase mutants of endo-D, an endo-beta-N-acetylglucosaminidase from Streptococcus pneumoniae. J Biol Chem 2012, 287 (14), 11272-81.

47. Manabe, S.; Yamaguchi, Y.; Matsumoto, K.; Fuchigami, H.; Kawase, T.; Hirose, K.; Mitani, A.; Sumiyoshi, W.; Kinoshita, T.; Abe, J.; Yasunaga, M.; Matsumura, Y.; Ito, Y., Characterization of Antibody Products Obtained through Enzymatic and Nonenzymatic Glycosylation Reactions with a Glycan Oxazoline and Preparation of a Homogeneous Antibody-Drug Conjugate via Fc N-Glycan. Bioconjug Chem 2019, 30 (5), 1343-1355.

48. Hojo, H.; Tanaka, H.; Hagiwara, M.; Asahina, Y.; Ueki, A.; Katayama, H.; Nakahara, Y.; Yoneshige, A.; Matsuda, J.; Ito, Y.; Nakahara, Y., Chemoenzymatic synthesis of hydrophobic glycoprotein: synthesis of saposin C carrying complex-type carbohydrate. J Org Chem 2012, 77 (21), 9437-46.

49. Asahina, Y.; Kamitori, S.; Takao, T.; Nishi, N.; Hojo, H., Chemoenzymatic synthesis of the immunoglobulin domain of Tim-3 carrying a complex-type N-glycan by using a one-pot ligation. Angew Chem Int Ed Engl 2013, 52 (37), 9733-7.

50. Agouridas, V.; El Mahdi, O.; Diemer, V.; Cargoet, M.; Monbaliu, J. M.; Melnyk, O., Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations. Chem Rev 2019, 119 (12), 7328-7443.

51. Dawson, P. E.; Kent, S. B., Synthesis of native proteins by chemical ligation. Annu Rev Biochem 2000, 69, 923-60.

52. Dawson, P. E.; Muir, T. W.; Clark-Lewis, I.; Kent, S. B., Synthesis of proteins by native chemical ligation. Science 1994, 266 (5186), 776-9.

53. Yan, L. Z.; Dawson, P. E., Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization. J Am Chem Soc 2001, 123 (4), 526-33.

54. Wan, Q.; Danishefsky, S. J., Free-radical-based, specific desulfurization of cysteine: a powerful advance in the synthesis of polypeptides and glycopolypeptides. Angew Chem Int Ed Engl 2007, 46 (48), 9248-52.

55. Thompson, R. E.; Chan, B.; Radom, L.; Jolliffe, K. A.; Payne, R. J., Chemoselective Peptide Ligation–Desulfurization at Aspartate. Angewandte Chemie International Edition 2013, 52 (37), 9723-9727.

56. Kulkarni, S. S.; Sayers, J.; Premdjee, B.; Payne, R. J., Rapid and efficient protein synthesis through expansion of the native chemical ligation concept. Nature Reviews Chemistry 2018, 2 (4), 0122.

57. Wong, C. T. T.; Tung, C. L.; Li, X., Synthetic cysteine surrogates used in native chemical ligation.Molecular BioSystems 2013, 9 (5), 826-833.

58. Merrifield, R. B., Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. Journal of the American Chemical Society 1963, 85 (14), 2149-2154.

59. Asahina, Y.; Komiya, S.; Ohagi, A.; Fujimoto, R.; Tamagaki, H.; Nakagawa, K.; Sato, T.; Akira, S.; Takao, T.; Ishii, A.; Nakahara, Y.; Hojo, H., Chemical Synthesis of O-Glycosylated Human Interleukin- 2 by the Reverse Polarity Protection Strategy. Angew Chem Int Ed Engl 2015, 54 (28), 8226-30.

60. Anisfeld, S. T.; Lansbury Jr, P. T., A convergent approach to the chemical synthesis of asparagine-linked glycopeptides. The Journal of Organic Chemistry 1990, 55 (21), 5560-5562.

61. Cohen-Anisfeld, S. T.; Lansbury, P. T., A practical, convergent method for glycopeptide synthesis.Journal of the American Chemical Society 1993, 115 (23), 10531-10537.

62. Ullmann, V.; Radisch, M.; Boos, I.; Freund, J.; Pohner, C.; Schwarzinger, S.; Unverzagt, C., Convergent solid-phase synthesis of N-glycopeptides facilitated by pseudoprolines at consensus-sequence Ser/Thr residues. Angew Chem Int Ed Engl 2012, 51 (46), 11566-70.

63. Wang, P.; Aussedat, B.; Vohra, Y.; Danishefsky, S. J., An advance in the chemical synthesis of homogeneous N-linked glycopolypeptides by convergent aspartylation. Angew Chem Int Ed Engl 2012, 51 (46), 11571-5.

64. Wang, P.; Li, X.; Zhu, J.; Chen, J.; Yuan, Y.; Wu, X.; Danishefsky, S. J., Encouraging progress in the omega-aspartylation of complex oligosaccharides as a general route to beta-N-linked glycopolypeptides. J Am Chem Soc 2011, 133 (5), 1597-602.

65. Joseph, R.; Dyer, F. B.; Garner, P., Rapid formation of N-Glycopeptides via Cu(II)-promoted glycosylative ligation. Org Lett 2013, 15 (4), 732-5.

66. Du, J. J.; Gao, X. F.; Xin, L. M.; Lei, Z.; Liu, Z.; Guo, J., Convergent Synthesis of N-Linked Glycopeptides via Aminolysis of omega-Asp p-Nitrophenyl Thioesters in Solution. Org Lett 2016, 18 (19), 4828-4831.

67. Schowe, M. J.; Keiper, O.; Unverzagt, C.; Wittmann, V., A Tripeptide Approach to the Solid- Phase Synthesis of Peptide Thioacids and N-Glycopeptides. Chemistry 2019, 25 (69), 15759-15764.

68. Chai, H.; Le Mai Hoang, K.; Vu, M. D.; Pasunooti, K.; Liu, C. F.; Liu, X. W., N-Linked Glycosyl Auxiliary-Mediated Native Chemical Ligation on Aspartic Acid: Application towards N-Glycopeptide Synthesis. Angew Chem Int Ed Engl 2016, 55 (35), 10363-7.

69. Maki, Y.; Okamoto, R.; Izumi, M.; Kajihara, Y., Chemical Synthesis of an Erythropoietin Glycoform Having a Triantennary N-Glycan: Significant Change of Biological Activity of Glycoprotein by Addition of a Small Molecular Weight Trisaccharide. J Am Chem Soc 2020, 142 (49), 20671-20679.

70. Wu, B.; Chen, J.; Warren, J. D.; Chen, G.; Hua, Z.; Danishefsky, S. J., Building complex glycopeptides: Development of a cysteine-free native chemical ligation protocol. Angew Chem Int Ed Engl 2006, 45 (25), 4116-25.

71. Brik, A.; Yang, Y. Y.; Ficht, S.; Wong, C. H., Sugar-assisted glycopeptide ligation. J Am Chem Soc 2006, 128 (17), 5626-7.

72. Chen, J.; Wan, Q.; Yuan, Y.; Zhu, J.; Danishefsky, S. J., Native chemical ligation at valine: a contribution to peptide and glycopeptide synthesis. Angew Chem Int Ed Engl 2008, 47 (44), 8521-4.

73. Payne, R. J.; Wong, C. H., Advances in chemical ligation strategies for the synthesis of glycopeptides and glycoproteins. Chem Commun (Camb) 2010, 46 (1), 21-43.

74. Shin, Y.; Winans, K. A.; Backes, B. J.; Kent, S. B. H.; Ellman, J. A.; Bertozzi, C. R., Fmoc-Based Synthesis of Peptide-αThioesters: Application to the Total Chemical Synthesis of a Glycoprotein by Native Chemical Ligation. Journal of the American Chemical Society 1999, 121 (50), 11684-11689.

75. Mezzato, S.; Schaffrath, M.; Unverzagt, C., An orthogonal double-linker resin facilitates the efficient solid-phase synthesis of complex-type N-glycopeptide thioesters suitable for native chemical ligation. Angew Chem Int Ed Engl 2005, 44 (11), 1650-4.

76. Yamamoto, N.; Tanabe, Y.; Okamoto, R.; Dawson, P. E.; Kajihara, Y., Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies. J Am Chem Soc 2008, 130 (2), 501-10.

77. Aussedat, B.; Fasching, B.; Johnston, E.; Sane, N.; Nagorny, P.; Danishefsky, S. J., Total synthesis of the alpha-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone. J Am Chem Soc 2012, 134 (7), 3532-41.

78. Murakami, M.; Okamoto, R.; Izumi, M.; Kajihara, Y., Chemical synthesis of an erythropoietin glycoform containing a complex-type disialyloligosaccharide. Angew Chem Int Ed Engl 2012, 51 (15), 3567-72.

79. Sakamoto, I.; Tezuka, K.; Fukae, K.; Ishii, K.; Taduru, K.; Maeda, M.; Ouchi, M.; Yoshida, K.; Nambu, Y.; Igarashi, J.; Hayashi, N.; Tsuji, T.; Kajihara, Y., Chemical synthesis of homogeneous human glycosyl-interferon-beta that exhibits potent antitumor activity in vivo. J Am Chem Soc 2012, 134 (12), 5428-31.

80. Okamoto, R.; Mandal, K.; Ling, M.; Luster, A. D.; Kajihara, Y.; Kent, S. B., Total chemical synthesis and biological activities of glycosylated and non-glycosylated forms of the chemokines CCL1 and Ser-CCL1. Angew Chem Int Ed Engl 2014, 53 (20), 5188-93.

81. Okamoto, R.; Mandal, K.; Sawaya, M. R.; Kajihara, Y.; Yeates, T. O.; Kent, S. B., (Quasi-)racemic X-ray structures of glycosylated and non-glycosylated forms of the chemokine Ser-CCL1 prepared by total chemical synthesis. Angew Chem Int Ed Engl 2014, 53 (20), 5194-8.

82. Murakami, M.; Kiuchi, T.; Nishihara, M.; Tezuka, K.; Okamoto, R.; Izumi, M.; Kajihara, Y., Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity. Sci Adv 2016, 2 (1), e1500678.

83. Minh Hien, N.; Izumi, M.; Sato, H.; Okamoto, R.; Kajihara, Y., Chemical Synthesis of Glycoproteins with the Specific Installation of Gradient-Enriched (15) N-Labeled Amino Acids for Getting Insights into Glycoprotein Behavior. Chemistry 2017, 23 (27), 6579-6585.

84. Li, H.; Zhang, J.; An, C.; Dong, S., Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms. J Am Chem Soc 2021, 143 (7), 2846-2856.

85. Muir, T. W.; Sondhi, D.; Cole, P. A., Expressed protein ligation: a general method for protein engineering. Proc Natl Acad Sci U S A 1998, 95 (12), 6705-10.

86. Muir, T. W., Semisynthesis of proteins by expressed protein ligation. Annu Rev Biochem 2003,72, 249-89.

87. Piontek, C.; Ring, P.; Harjes, O.; Heinlein, C.; Mezzato, S.; Lombana, N.; Pohner, C.; Puttner, M.; Varon Silva, D.; Martin, A.; Schmid, F. X.; Unverzagt, C., Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 1. Angew Chem Int Ed Engl 2009, 48 (11), 1936-40.

88. Piontek, C.; Varon Silva, D.; Heinlein, C.; Pohner, C.; Mezzato, S.; Ring, P.; Martin, A.; Schmid,F. X.; Unverzagt, C., Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 2. Angew Chem Int Ed Engl 2009, 48 (11), 1941-5.

89. Okamoto, R.; Kimura, M.; Ishimizu, T.; Izumi, M.; Kajihara, Y., Semisynthesis of a post- translationally modified protein by using chemical cleavage and activation of an expressed fusion polypeptide. Chemistry 2014, 20 (33), 10425-30.

90. Okamoto, R.; Iritani, K.; Amazaki, Y.; Zhao, D.; Chandrashekar, C.; Maki, Y.; Kanemitsu, Y.; Kaino, T.; Kajihara, Y., Semisynthesis of a Homogeneous Glycoprotein Using Chemical Transformation of Peptides to Thioester Surrogates. J Org Chem 2022, 87 (1), 114-124.

91. Ludwig, C.; Schwarzer, D.; Zettler, J.; Garbe, D.; Janning, P.; Czeslik, C.; Mootz, H. D., Semisynthesis of proteins using split inteins. Methods Enzymol 2009, 462, 77-96.

92. Ling, J. J.; Policarpo, R. L.; Rabideau, A. E.; Liao, X.; Pentelute, B. L., Protein thioester synthesis enabled by sortase. J Am Chem Soc 2012, 134 (26), 10749-52.

93. Komiya, C.; Shigenaga, A.; Tsukimoto, J.; Ueda, M.; Morisaki, T.; Inokuma, T.; Itoh, K.; Otaka, A., Traceless synthesis of protein thioesters using enzyme-mediated hydrazinolysis and subsequent self- editing of the cysteinyl prolyl sequence. Chem Commun (Camb) 2019, 55 (49), 7029-7032.

94. Okamoto, R.; Morooka, K.; Kajihara, Y., A synthetic approach to a peptide alpha-thioester from an unprotected peptide through cleavage and activation of a specific peptide bond by N-acetylguanidine. Angew Chem Int Ed Engl 2012, 51 (1), 191-6.

95. Kajihara, Y.; Kanemitsu, Y.; Nishihara, M.; Okamoto, R.; Izumi, M., Efficient synthesis of polypeptide-alpha-thioester by the method combining polypeptide expression and chemical activation for the semi-synthesis of interferon-gamma having oligosaccharides. J Pept Sci 2014, 20 (12), 958-63.

96. Kawakami, T.; Sumida, M.; Nakamura, K. i.; Vorherr, T.; Aimoto, S., Peptide thioester preparation based on an N-S acyl shift reaction mediated by a thiol ligation auxiliary. Tetrahedron Letters 2005, 46 (50), 8805-8807.

97. Nakamura, K. i.; Sumida, M.; Kawakami, T.; Vorherr, T.; Aimoto, S., Generation of an S-Peptide via an N–S Acyl Shift Reaction in a TFA Solution. Bulletin of the Chemical Society of Japan 2006, 79 (11), 1773-1780.

98. Kang, J.; Macmillan, D., Peptide and protein thioester synthesis via N→S acyl transfer. Organic & Biomolecular Chemistry 2010, 8 (9), 1993-2002.

99. N, N.; Thimmalapura, V. M.; Hosamani, B.; Prabhu, G.; Kumar, L. R.; Sureshbabu, V. V., Thioacids – synthons for amide bond formation and ligation reactions: assembly of peptides and peptidomimetics. Organic & Biomolecular Chemistry 2018, 16 (19), 3524-3552.

100. Crich, D.; Sharma, I., Epimerization-free block synthesis of peptides from thioacids and amines with the Sanger and Mukaiyama reagents. Angew Chem Int Ed Engl 2009, 48 (13), 2355-8.

101. Sasaki, K.; Crich, D., Cyclic peptide synthesis with thioacids. Org Lett 2010, 12 (14), 3254-7.

102. Song, W.; Dong, K.; Li, M., Visible Light-Induced Amide Bond Formation. Org Lett 2020, 22(2), 371-375.

103. Pan, J.; Devarie-Baez, N. O.; Xian, M., Facile amide formation via S-nitrosothioacids. Org Lett2011, 13 (5), 1092-4.

104. Wu, W.; Zhang, Z.; Liebeskind, L. S., In situ carboxyl activation using a silatropic switch: a new approach to amide and peptide constructions. J Am Chem Soc 2011, 133 (36), 14256-9.

105. Wu, X.; Stockdill, J. L.; Park, P. K.; Danishefsky, S. J., Expanding the limits of isonitrile- mediated amidations: on the remarkable stereosubtleties of macrolactam formation from synthetic seco- cyclosporins. J Am Chem Soc 2012, 134 (4), 2378-84.

106. Shangguan, N.; Katukojvala, S.; Greenberg, R.; Williams, L. J., The reaction of thio acids with azides: a new mechanism and new synthetic applications. J Am Chem Soc 2003, 125 (26), 7754-5.

107. Kolakowski, R. V.; Shangguan, N.; Sauers, R. R.; Williams, L. J., Mechanism of thio acid/azide amidation. J Am Chem Soc 2006, 128 (17), 5695-702.

108. Rohmer, K.; Mannuthodikayil, J.; Wittmann, V., Application of the Thioacid-Azide Ligation (TAL) for the Preparation of Glycosylated and Fluorescently Labeled Amino Acids. Israel Journal of Chemistry 2015, 55 (3-4), 437-446.

109. Dyer, F. B.; Park, C. M.; Joseph, R.; Garner, P., Aziridine-mediated ligation and site-specific modification of unprotected peptides. J Am Chem Soc 2011, 133 (50), 20033-5.

110. Bajaj, K.; Agarwal, D. S.; Sakhuja, R.; Pillai, G. G., Aziridine based electrophilic handle for aspartic acid ligation. Org Biomol Chem 2018, 16 (23), 4311-4319.

111. Crich, D.; Sana, K.; Guo, S., Amino acid and peptide synthesis and functionalization by the reaction of thioacids with 2,4-dinitrobenzenesulfonamides. Org Lett 2007, 9 (22), 4423-6.

112. Crich, D.; Sharma, I., Triblock peptide and peptide thioester synthesis with reactivity-differentiated sulfonamides and peptidyl thioacids. Angew Chem Int Ed Engl 2009, 48 (41), 7591-4.

113. Fukuyama, T.; Jow, C.-K.; Cheung, M., 2- and 4-Nitrobenzenesulfonamides: Exceptionally versatile means for preparation of secondary amines and protection of amines. Tetrahedron Letters 1995, 36 (36), 6373-6374.

114. Chen, W.; Shao, J.; Hu, M.; Yu, W.; Giulianotti, M. A.; Houghten, R. A.; Yu, Y., A traceless approach to amide and peptide construction from thioacids and dithiocarbamate-terminal amines. Chem. Sci. 2013, 4 (3), 970-976.

115. Crich, D.; Sasaki, K., Reaction of thioacids with isocyanates and isothiocyanates: a convenient amide ligation process. Org Lett 2009, 11 (15), 3514-7.

116. Tam, J. P.; Lu, Y. A.; Liu, C. F.; Shao, J., Peptide synthesis using unprotected peptides through orthogonal coupling methods. Proc Natl Acad Sci U S A 1995, 92 (26), 12485-9.

117. Zhang, X.; Li, F.; Liu, C. F., Synthesis of histone H3 proteins by a thioacid capture ligation strategy. Chem Commun (Camb) 2011, 47 (6), 1746-8.

118. Okamoto, R.; Haraguchi, T.; Nomura, K.; Maki, Y.; Izumi, M.; Kajihara, Y., Regioselective alpha-Peptide Bond Formation Through the Oxidation of Amino Thioacids. Biochemistry 2019, 58 (12), 1672-1678.

119. Okamoto, R.; Nomura, K.; Maki, Y.; Kajihara, Y., A Chemoselective Peptide Bond Formation by Amino Thioacid Coupling. Chemistry Letters 2019, 48 (11), 1391-1393.

120. Nomura, K.; Maki, Y.; Okamoto, R.; Satoh, A.; Kajihara, Y., Glycoprotein Semisynthesis by Chemical Insertion of Glycosyl Asparagine Using a Bifunctional Thioacid-Mediated Strategy. J Am Chem Soc 2021, 143 (27), 10157-10167.

121. Kato, M.; Uno, T.; Hiratake, J.; Sakata, K., alpha-Glucopyranoimidazolines as intermediate analogue inhibitors of family 20 beta-N-acetylglucosaminidases. Bioorg Med Chem 2005, 13 (5), 1563-71.

122. Ibatullin, F. M.; Selivanov, S. I., Reaction of N-Fmoc aspartic anhydride with glycosylamines: a simple entry to N-glycosyl asparagines. Tetrahedron Letters 2009, 50 (46), 6351-6354.

123. Liu, R.; Orgel, L. E., Oxidative acylation using thioacids. Nature 1997, 389 (6646), 52-4.

124. Wang, P.; Danishefsky, S. J., Promising general solution to the problem of ligating peptides and glycopeptides. J Am Chem Soc 2010, 132 (47), 17045-51.

125. Dery, S.; Reddy, P. S.; Dery, L.; Mousa, R.; Dardashti, R. N.; Metanis, N., Insights into the deselenization of selenocysteine into alanine and serine. Chem Sci 2015, 6 (11), 6207-6212.

126. Premdjee, B.; Andersen, A. S.; Larance, M.; Conde-Frieboes, K. W.; Payne, R. J., Chemical Synthesis of Phosphorylated Insulin-like Growth Factor Binding Protein 2. J Am Chem Soc 2021, 143 (14), 5336-5342.

127. Koide, T.; Itoh, H.; Otaka, A.; Yasui, H.; Kuroda, M.; Esaki, N.; Soda, K.; Fujii, N., Synthetic study on selenocystine-containing peptides. Chem Pharm Bull (Tokyo) 1993, 41 (3), 502-6.

128. Harris, K. M.; Flemer Jr, S.; Hondal, R. J., Studies on deprotection of cysteine and selenocysteine side-chain protecting groups. Journal of Peptide Science 2007, 13 (2), 81-93.

129. Mali, S. M.; Gopi, H. N., Thioacetic Acid/NaSH-Mediated Synthesis of N-Protected Amino Thioacids and Their Utility in Peptide Synthesis. The Journal of Organic Chemistry 2014, 79 (6), 2377- 2383.

130. Luster, A. D., Chemokines--chemotactic cytokines that mediate inflammation. N Engl J Med 1998, 338 (7), 436-45.

131. Koenen, R. R.; Weber, C., Therapeutic targeting of chemokine interactions in atherosclerosis.Nat Rev Drug Discov 2010, 9 (2), 141-53.

132. Miller, M. C.; Mayo, K. H., Chemokines from a Structural Perspective. Int J Mol Sci 2017, 18(10), 2088.

133. Baggiolini, M.; Dewald, B.; Moser, B., Human chemokines: an update. Annu Rev Immunol 1997,15, 675-705.

134. Haskell, C. A.; Cleary, M. D.; Charo, I. F., Unique role of the chemokine domain of fractalkine in cell capture. Kinetics of receptor dissociation correlate with cell adhesion. J Biol Chem 2000, 275 (44), 34183-9.

135. Izumi, M.; Murakami, M.; Okamoto, R.; Kajihara, Y., Safe and efficient Boc-SPPS for the synthesis of glycopeptide-α-thioesters. Journal of Peptide Science 2014, 20 (2), 98-101.

136. Simon, M. D.; Heider, P. L.; Adamo, A.; Vinogradov, A. A.; Mong, S. K.; Li, X.; Berger, T.; Policarpo, R. L.; Zhang, C.; Zou, Y.; Liao, X.; Spokoyny, A. M.; Jensen, K. F.; Pentelute, B. L., Rapid Flow- Based Peptide Synthesis. ChemBioChem 2014, 15 (5), 713-720.

137. Kajihara, Y.; Nishikawa, R.; Maki, Y.; Okamoto, R., Studies in glycopeptide synthesis.ARKIVOC 2020, 2021 (4), 230-240.

138. Liu, H.; Li, X., Serine/Threonine Ligation: Origin, Mechanistic Aspects, and Applications.Accounts of Chemical Research 2018, 51 (7), 1643-1655.

139. Jbara, M.; Laps, S.; Morgan, M.; Kamnesky, G.; Mann, G.; Wolberger, C.; Brik, A., Palladium prompted on-demand cysteine chemistry for the synthesis of challenging and uniquely modified proteins. Nature Communications 2018, 9 (1), 3154.

140. Maity, S. K.; Jbara, M.; Laps, S.; Brik, A., Efficient Palladium-Assisted One-Pot Deprotection of (Acetamidomethyl)Cysteine Following Native Chemical Ligation and/or Desulfurization To Expedite Chemical Protein Synthesis. Angewandte Chemie International Edition 2016, 55 (28), 8108-8112.

141. Yang, Y.-C.; Ciarletta, A. B.; Temple, P. A.; Chung, M. P.; Kovacic, S.; Witek-Giannotti, J. S.; Leary, A. C.; Kriz, R.; Donahue, R. E.; Wong, G. G.; Clark, S. C., Human IL-3 (multi-CSF): Identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell 1986, 47 (1), 3- 10.

142. Schweiger, A.; Stern, D.; Lohman, I. C.; Baldini, M.; Martinez, F. D.; Halonen, M., Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3. J Allergy Clin Immunol 2001, 107 (3), 505-10.

143. Urdal, D. L.; Price, V.; Sassenfeld, H. M.; Cosman, D.; Gillis, S.; Park, L. S., Molecular characterization of colony-stimulating factors and their receptors: human interleukin-3. Ann N Y Acad Sci 1989, 554, 167-76.

144. Cheng, H.; Zheng, Z.; Cheng, T., New paradigms on hematopoietic stem cell differentiation.Protein Cell 2020, 11 (1), 34-44.

145. Robb, L., Cytokine receptors and hematopoietic differentiation. Oncogene 2007, 26 (47), 6715-23.

146. Socolovsky, M.; Lodish, H. F.; Daley, G. Q., Control of hematopoietic differentiation: lack of specificity in signaling by cytokine receptors. Proc Natl Acad Sci U S A 1998, 95 (12), 6573-5.

147. Katayama, H.; Morisue, S., A novel ring opening reaction of peptide N-terminal thiazolidine with 2,2′-dipyridyl disulfide (DPDS) efficient for protein chemical synthesis. Tetrahedron 2017, 73 (25), 3541-3547.

148. Matveenko, M.; Hackl, S.; Becker, C. F. W., Utility of the Phenacyl Protecting Group in Traceless Protein Semisynthesis through Ligation-Desulfurization Chemistry. ChemistryOpen 2018, 7 (1), 106-110.

149. McElroy, C. A.; Dohm, J. A.; Walsh, S. T. R., Structural and biophysical studies of the human IL-7/IL-7Ralpha complex. Structure 2009, 17 (1), 54-65.

150. Lun, Y. Z.; Wang, X. L.; Feng, J., Purification and identification of the Kazal domain of a novel serine protease inhibitor, Hespintor, through a bacterial (Escherichia coli) expression system. Int J Mol Med 2014, 34 (1), 321-6.

151. Cai, S.; Zhang, P.; Dong, S.; Li, L.; Cai, J.; Xu, M., Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells. Cell Physiol Biochem 2018, 45 (3), 1061-1071.

152. Wei, L.; Lun, Y.; Zhou, X.; He, S.; Gao, L.; Liu, Y.; He, Z.; Li, B.; Wang, C., Novel urokinase- plasminogen activator inhibitor SPINK13 inhibits growth and metastasis of hepatocellular carcinoma in vivo. Pharmacol Res 2019, 143, 73-85.

153. Xu, W. H.; Shi, S. N.; Wang, J.; Xu, Y.; Tian, X.; Wan, F. N.; Cao, D. L.; Qu, Y. Y.; Zhang, H. L.;Ye, D. W., The Role of Serine Peptidase Inhibitor Kazal Type 13 (SPINK13) as a Clinicopathological and Prognostic Biomarker in Patients with Clear Cell Renal Cell Carcinoma. Med Sci Monit 2019, 25, 9458- 9470.

154. Bause, E.; Hettkamp, H., Primary structural requirements for N-glycosylation of peptides in rat liver. FEBS Lett 1979, 108 (2), 341-4.

155. Pitti, T.; Chen, C. T.; Lin, H. N.; Choong, W. K.; Hsu, W. L.; Sung, T. Y., N-GlyDE: a two-stage N-linked glycosylation site prediction incorporating gapped dipeptides and pattern-based encoding. Sci Rep 2019, 9 (1), 15975.

156. Nakamura, T.; Shigenaga, A.; Sato, K.; Tsuda, Y.; Sakamoto, K.; Otaka, A., Examination of native chemical ligation using peptidyl prolyl thioesters. Chem Commun (Camb) 2014, 50 (1), 58-60.

157. Durek, T.; Alewood, P. F., Preformed selenoesters enable rapid native chemical ligation at intractable sites. Angew Chem Int Ed Engl 2011, 50 (50), 12042-5.

158. Raibaut, L.; Seeberger, P.; Melnyk, O., Bis(2-sulfanylethyl)amido peptides enable native chemical ligation at proline and minimize deletion side-product formation. Org Lett 2013, 15 (21), 5516-9.

159. Kawakami, T.; Aimoto, S., The use of a cysteinyl prolyl ester (CPE) autoactivating unit in peptide ligation reactions. Tetrahedron 2009, 65 (19), 3871-3877.

160. Matsumoto, T.; Sasamoto, K.; Hirano, R.; Oisaki, K.; Kanai, M., A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin via iterative peptide-fragment coupling reactions. Chem Commun (Camb) 2018, 54 (86), 12222-12225.

161. Sureshbabu, V.; Vishwanatha, T.; Samarasimhareddy, M., Facile N-Urethane-Protected α- Amino/Peptide Thioacid Preparation Using EDC and Na2S. Synlett 2011, 2012 (01), 89-92.

162. Sureshbabu, V.; Madhu, C.; Vishwanatha, T., An Efficient Synthesis of Nα-Protected Amino and Peptide Acid Aryl Amides via Iodine-Mediated Oxidative Acylation of Nα-Protected Amino and Peptide Thioacids. Synthesis 2013, 45 (19), 2727-2736.

163. Chen, C.; Huang, Y.; Xu, L.; Zheng, Y.; Xu, H.; Guo, Q.; Tian, C.; Li, Y.; Shi, J., Thiol-assisted one-pot synthesis of peptide/protein C-terminal thioacids from peptide/protein hydrazides at neutral conditions. Org Biomol Chem 2014, 12 (46), 9413-8.

164. Elagawany, M.; Hegazy, L.; Elgendy, B., Catalyst- and organic solvent-free synthesis of thioacids in water. Tetrahedron Letters 2019, 60 (30), 2018-2021.

165. Katritzky, A.; Khaybullin, R.; Panda, S.; Al-Youbi, A., A Facile Synthesis of Thioacids from N- Acylbenzotriazoles. Synlett 2013, 25 (02), 247-250.

166. Kinsland, C.; Taylor, S. V.; Kelleher, N. L.; McLafferty, F. W.; Begley, T. P., Overexpression of recombinant proteins with a C-terminal thiocarboxylate: implications for protein semisynthesis and thiamin biosynthesis. Protein Sci 1998, 7 (8), 1839-42.

167. Barkan, D.; Green, J. E.; Chambers, A. F., Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. Eur J Cancer 2010, 46 (7), 1181-8.

168. Mahmood, N.; Mihalcioiu, C.; Rabbani, S. A., Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications. Front Oncol 2018, 8, 24.

169. Pillay, V.; Dass, C. R.; Choong, P. F. M., The urokinase plasminogen activator receptor as a gene therapy target for cancer. Trends in Biotechnology 2007, 25 (1), 33-39.

170. Jabłońska-Trypuć, A.; Matejczyk, M.; Rosochacki, S., Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem 2016, 31 (sup1), 177-183.

171. Stanton, H.; Gavrilovic, J.; Atkinson, S. J.; d'Ortho, M. P.; Yamada, K. M.; Zardi, L.; Murphy, G., The activation of ProMMP-2 (gelatinase A) by HT1080 fibrosarcoma cells is promoted by culture on a fibronectin substrate and is concomitant with an increase in processing of MT1-MMP (MMP-14) to a 45 kDa form. J Cell Sci 1998, 111 ( Pt 18), 2789-98.

172. Jumper, J.; Evans, R.; Pritzel, A.; Green, T.; Figurnov, M.; Ronneberger, O.; Tunyasuvunakool, K.; Bates, R.; Žídek, A.; Potapenko, A.; Bridgland, A.; Meyer, C.; Kohl, S. A. A.; Ballard, A. J.; Cowie, A.; Romera-Paredes, B.; Nikolov, S.; Jain, R.; Adler, J.; Back, T.; Petersen, S.; Reiman, D.; Clancy, E.; Zielinski, M.; Steinegger, M.; Pacholska, M.; Berghammer, T.; Bodenstein, S.; Silver, D.; Vinyals, O.; Senior, A. W.; Kavukcuoglu, K.; Kohli, P.; Hassabis, D., Highly accurate protein structure prediction with AlphaFold. Nature 2021, 596 (7873), 583-589.

173. Izumi, M.; Murakami, M.; Okamoto, R.; Kajihara, Y., Safe and efficient Boc-SPPS for the synthesis of glycopeptide-alpha-thioesters. J Pept Sci 2014, 20 (2), 98-101.

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