Citation: Zhang Chong, Lu Hua. Efficient Synthesis and Application of Protein-Poly(α-amino acid) Conjugates[J]. Acta Polymerica Sinica, ;2018, (1): 21-31. doi: 10.11777/j.issn1000-3304.2018.17204 shu

Efficient Synthesis and Application of Protein-Poly(α-amino acid) Conjugates

Zhang Chong ,
Lu Hua ^,

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871

Corresponding author: Lu Hua, chemhualu@pku.edu.cn
Received Date: 28 July 2017
Revised Date: 22 September 2017

Protein-polymer conjugates are important therapeutics for various diseases. There are currently two major challenges in this field: one is the search of new biodegradable polymers beyond traditional PEGylation, and the other is to develop highly efficient and site-specific conjugation strategy. Poly(α-amino acid)s (PαAAs) are biodegradable and biocompatible polymers with tunable properties and numerous functions, making them promising candidates for protein modification. In this review, we summarize our recent progresses in protein-PαAAs conjugates. Specifically, we discuss our developments in: (1) Recent developments in the controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs), including amine-based initiators, organometallic initiators, organosilicon amines initiators and sulfide-based initiators. For instance, trimethylsilyl phenylsulfide (PhSTMS) is a novel initiator for controlled ROP of NCAs. It exhibits higher nucleophilicity than conventional amine-based initiator, and thus affords considerably higher chain initiation rate to ensure a more controlled polymerization. Moreover, this initiator is well-tolerated to various functional groups. (2) In situ functionalization of PαAAs for site-specific protein conjugation, and construction of various topological structures. Using PhSTMS initiator, it in situ generates a reactive phenyl thioester group at one end of the PαAAs, which can be used for protein N-terminus conjugation via native chemical ligation (NCL); moreover, ROP of glycine NCA yields oligoglycine at the other end of PαAAs, which can be used for C-terminus protein conjugation via sortase-A mediated ligation (SML). More interestingly, combinatory use of the two methods can construct various topological protein-PαAA conjugates including the head-to-tail circular conjugates. (3) Development of functional PαAAs for potential protein conjugation. Various functional PαAAs have been developed as delivery materials or hydrogels. To further expand the arsenal of PαAAs for potential modulation of protein functions, PαAAs that mimic protein post-translational modifications (PTM) are synthesized; On the other hand, a series of multiple stimuli-responsive PαAAs are also produced. These PαAAs show interesting enzyme, light, and/or thermal responsiveness, which could be potentially harnessed for modulation of protein functions in the future.
- Protein conjugation,
- Poly(α-amino acid),
- PTM mimicking,
- Topology,
- Stimuli-responsiveness
1. [1]
  Swinney D C, Anthony J. Nat Rev Drug Discov, 2011, 10(7):507-519 doi: 10.1038/nrd3480
2. [2]
  Abuchowski A, Vanes T, Palczuk N C, Davis F F. J Biol Chem, 1977, 252(11):3578-3581
3. [3]
  Alconcel S N S, Baas A S, Maynard H D. Polym Chem, 2011, 2(7):1442-1448 doi: 10.1039/c1py00034a
4. [4]
  Schellekens H, Hennink W E, Brinks V. Pharm Res, 2013, 30(7):1729-1734 doi: 10.1007/s11095-013-1067-7
5. [5]
  Gauthier M A, Klok H A. Polym Chem, 2010, 1(9):1352-1373 doi: 10.1039/c0py90001j
6. [6]
  Kochendoerfer G G. Curr Opin Chem Biol, 2005, 9(6):555-560 doi: 10.1016/j.cbpa.2005.10.007
7. [7]
  Pelegri-O'Day E M, Lin E W, Maynard H D. J Am Chem Soc, 2014, 136(41):14323-14332 doi: 10.1021/ja504390x
8. [8]
  Knop K, Hoogenboom R, Fischer D, Schubert U S. Angew Chem Int Ed, 2010, 49(36):6288-6308 doi: 10.1002/anie.200902672
9. [9]
  Bontempo D, Maynard H D. J Am Chem Soc, 2005, 127(18):6508-6509 doi: 10.1021/ja042230+
10. [10]
  Gao W, Liu W, Mackay J A, Zalutsky M R, Toone E J, Chilkoti A. Proc Natl Acad Sci USA, 2009, 106(36):15231-15236 doi: 10.1073/pnas.0904378106
11. [11]
  Boyer C, Bulmus V, Liu J, Davis T P, Stenzel M H, Barner-Kowollik C. J Am Chem Soc, 2007, 129(22):7145-7154 doi: 10.1021/ja070956a
12. [12]
  Hu J, Zhao W, Gao Y, Sun M, Wei Y, Deng H, Gao W. Biomaterials, 2015, 47:13-19 doi: 10.1016/j.biomaterials.2015.01.002
13. [13]
  Cho H, Daniel T, Buechler Y J, Litzinger D C, Maio Z, Putnam A M H, Kraynov V S, Sim B C, Bussell S, Javahishvili T, Kaphle S, Viramontes G, Ong M, Chu S, Becky G C, Lieu R, Knudsen N, Castiglioni P, Norman T C, Axelrod D W, Hoffman A R, Schultz P G, DiMarchi R D, Kimme B E. Proc Natl Acad Sci USA, 2011, 108(22):9060-9065 doi: 10.1073/pnas.1100387108
14. [14]
  Kochendoerfer G G, Chen S Y, Mao F, Cressman S, Traviglia S, Shao H Y, Hunter C L, Low D W, Cagle E N, Carnevali M, Gueriguian V, Keogh P J, Porter H, Stratton S M, Wiedeke M C, Wilken J, Tang J, Levy J J, Miranda L P, Crnogorac M M, Kalbag S, Botti P, Schindler-Horvat J, Savatski L, Adamson J W, Kung A, Kent S B H, Bradburne J A. Science, 2003, 299:884-887 doi: 10.1126/science.1079085
15. [15]
  Dumas A, Spicer C D, Gao Z, Takehana T, Lin Y A, Yasukohchi T, Davis B G. Angew Chem Int Ed, 2013, 52(14):3916-3921 doi: 10.1002/anie.v52.14
16. [16]
  Zhang B, Xu H, Chen J, Zheng Y, Wu Y, Si L, Wu L, Zhang C, Xia G, Zhang L, Zhou D. Acta Biomater, 2015, 19:100-111 doi: 10.1016/j.actbio.2015.03.002
17. [17]
  Biedermann F, Rauwald U, Zayed J M, Scherman O A. Chem Sci, 2011, 2(2):279-286 doi: 10.1039/C0SC00435A
18. [18]
  Cao L, Shi X, Cui Y, Yang W, Chen G, Yuan L, Chen H. Polym Chem, 2016, 7(32):5139-5146 doi: 10.1039/C6PY00882H
19. [19]
  Barz M, Luxenhofer R, Zentel R, Vicent M J. Polym Chem, 2011, 2(9):1900-1918 doi: 10.1039/c0py00406e
20. [20]
  Merrifield R B. J Am Chem Soc, 1963, 85(14):2149-2154 doi: 10.1021/ja00897a025
21. [21]
  Tao Youhua. Acta Polymerica Sinica, 2016, (9):1151-1159
22. [22]
  Huang J, Heise A. Chem Soc Rev, 2013, 42(17):7373-7390 doi: 10.1039/c3cs60063g
23. [23]
  Wang Mingzhi, Du Jianzhong. Acta Polymerica Sinica, 2014, (9):1183-1194
24. [24]
  Cheng J, Deming T J. Topics in Current Chemistry. Springer Berlin Heidelberg, 2012, 310: 1-26
25. [25]
  Leuchs H. Chem Ber, 1906, 39:857-861 doi: 10.1002/(ISSN)1099-0682
26. [26]
  Deming T J. Nature, 1997, 390(6658):386-389 doi: 10.1038/37084
27. [27]
  Deming T J. J Am Chem Soc, 1998, 120(17):4240-4241 doi: 10.1021/ja980313i
28. [28]
  Dimitrov I, Schlaad H. Chem Commun, 2003, 23:2944-2945
29. [29]
  Conejos-Sánchez I, Duro-Castano A, Birke A, Barz M, Vicent M J. Polym Chem, 2013, 4(11):3182-3186 doi: 10.1039/c3py00347g
30. [30]
  Peng Y, Lai S, Lin C. Macromolecules, 2008, 41(10):3455-3459 doi: 10.1021/ma7025836
31. [31]
  Peng H, Ling J, Shen Z. J Polym Sci, Part A:Polym Chem, 2012, 50(6):1076-1085 doi: 10.1002/pola.v50.6
32. [32]
  Aliferis T, Iatrou H, Hadjichristidis N. Biomacromolecules, 2004, 5(5):1653-1656 doi: 10.1021/bm0497217
33. [33]
  Zhao W, Gnanou Y, Hadjichristidis N. Biomacromolecules, 2015, 16(4):1352-1357 doi: 10.1021/acs.biomac.5b00134
34. [34]
  Zhao W, Gnanou Y, Hadjichristidis N. Polym Chem, 2015, 6(34):6193-6201 doi: 10.1039/C5PY00874C
35. [35]
  Li P, Dong C. ACS Macro Lett, 2017, 6(3):292-297 doi: 10.1021/acsmacrolett.7b00167
36. [36]
  Lu H, Cheng J. J Am Chem Soc, 2007, 129(46):14114-14115 doi: 10.1021/ja074961q
37. [37]
  Lu H, Cheng J. J Am Che Soc, 2008, 130(38):12562-12563 doi: 10.1021/ja803304x
38. [38]
  Lu H, Wang J, Lin Y, Cheng J. J Am Chem Soc, 2009, 131(38):13582-13583 doi: 10.1021/ja903425x
39. [39]
  Bai Y, Lu H, Ponnusamy E, Cheng J. Chem Commun, 2011, 47(38):10830-10832 doi: 10.1039/c1cc13531g
40. [40]
  Baumgartner R, Fu H, Song Z, Lin Y, Cheng J. Nat Chem, 2017, 9(7):614-622 doi: 10.1038/nchem.2712
41. [41]
  Yuan J, Sun Y, Wang J, Lu H. Biomacromolecules, 2016, 17(3):891-896 doi: 10.1021/acs.biomac.5b01588
42. [42]
  Grotzky A, Manaka Y, Kojima T, Walde P. Biomacromolecules, 2010, 12(1):134144
43. [43]
  Talelli M, Vicent M J. Biomacromolecules, 2014, 15(11):4168-4177 doi: 10.1021/bm5011883
44. [44]
  Hou Y, Yuan J, Zhou Y, Yu J, Lu H. J Am Chem Soc, 2016, 138(34):10995-11000 doi: 10.1021/jacs.6b05413
45. [45]
  Deng C, Wu J, Cheng R, Meng F, Klok H A, Zhong Z. Prog Polym Sci, 2014, 39(2):330-364 doi: 10.1016/j.progpolymsci.2013.10.008
46. [46]
  Lu H, Wang J, Song Z, Yin L, Zhang Y, Tang H, Tu C, Lin Y, Cheng J. Chem Commun, 2014, 50(2):139-155 doi: 10.1039/C3CC46317F
47. [47]
  Walsh C T, Garneau-Tsodikova S, Gatto G J. Angew Chem Int Ed, 2005, 44(45):7342-7372 doi: 10.1002/(ISSN)1521-3773
48. [48]
  Kramer J R, Deming T J. Polym Chem, 2014, 5(3):671-682 doi: 10.1039/C3PY01081C
49. [49]
  Pratt M R, Bertozzi C R. Chem Soc Rev, 2005, 34(1):58-68 doi: 10.1039/b400593g
50. [50]
  Pati D, Shaikh A Y, Das S, Nareddy P K, Swamy M J, Hotha S, Gupta S S. Biomacromolecules, 2012, 13(5):1287-1295 doi: 10.1021/bm201813s
51. [51]
  Rubin C S, Rosen O M. Annu Rev Biochem, 1975, 44(1):831-887 doi: 10.1146/annurev.bi.44.070175.004151
52. [52]
  Sun Y, Hou Y, Zhou X, Yuan J, Wang J, Lu H. ACS Macro Lett, 2015, 4(9):1000-1003 doi: 10.1021/acsmacrolett.5b00429
53. [53]
  Li S, Hou Y, Hu Y, Yu J, Wei W, Lu H. Biomater Sci, 2017, 5:1558-1566 doi: 10.1039/C6BM00935B
54. [54]
  Hou Y, Wang Y, Wang R, Bao W, Xi X, Sun Y, Lu H. ACS Appl Mater Interfaces, 2017, 9(21):17757-17768 doi: 10.1021/acsami.7b03686
55. [55]
  Shen Y, Fu X, Fu W, Li Z. Chem Soc Rev, 2015, 44(3):612-622 doi: 10.1039/C4CS00271G
56. [56]
  Yuan Jingsong, Lu Hua. Polym Bull, 2015, (9):210-216
57. [57]
  Chen C, Wang Z, Li Z. Biomacromolecules, 2011, 12(8):2859-2863 doi: 10.1021/bm200849m
58. [58]
  Fu X, Ma Y, Sun J, Li Z. Chinese J Polym Sci, 2016, 34(12):1436-1447 doi: 10.1007/s10118-016-1861-x
59. [59]
  Zhang S, Chen C, Li Z. Chinese J Polym Sci, 2013, 2(31):201-210
60. [60]
  Ge C, Liu S, Liang C, Ling Y, Tang H. Polym Chem, 2016, 7(38):5978-5987 doi: 10.1039/C6PY01287F
61. [61]
  Shi F, Ding J, Xiao C, Zhuang X, He C, Chen L, Chen X. J Mater Chem, 2012, 22(28):14168-14179 doi: 10.1039/c2jm32033a
62. [62]
  Wang K, Luo G, Liu Y, Li C, Cheng S, Zhuo R, Zhang X. Polym Chem, 2012, 3(4):1084-1090 doi: 10.1039/c2py00600f
63. [63]
  Kramer J R, Deming T J. J Am Chem Soc, 2012, 134(9):4112-4115 doi: 10.1021/ja3007484
64. [64]
  Chen P, Qiu M, Deng C, Meng F, Zhang J, Cheng R, Zhong Z. Biomacromolecules, 2015, 16(4):1322-1330 doi: 10.1021/acs.biomac.5b00113
65. [65]
  Lee E S, Oh K T, Kim D, Youn Y S, Bae Y H. J Control Release, 2007, 123(1):19-26 doi: 10.1016/j.jconrel.2007.08.006
66. [66]
  Rodríguez-Hernández J, Lecommandoux S. J Am Chem Soc, 2005, 127(7):2026-2027 doi: 10.1021/ja043920g
67. [67]
  Bae Y, Fukushima S, Harada A, Kataoka K. Angew Chem Int Ed, 2003, 42(38):4640-4643 doi: 10.1002/(ISSN)1521-3773
68. [68]
  Kotharangannagari V K, Sánchez-Ferrer A, Ruokolainen J, Mezzenga R. Macromolecules, 2011, 44(12):4569 -4573 doi: 10.1021/ma2008145
69. [69]
  Liu G, Dong C. Biomacromolecules, 2012, 13(5):1573-1583 doi: 10.1021/bm300304t
70. [70]
  Yin L, Tang H, Kim K H, Zheng N, Song Z, Gabrielson N P, Lu H, Cheng J. Angew Chem Int Ed, 2013, 52(35):9182-9186 doi: 10.1002/anie.201302820
71. [71]
  Xiong W, Fu X, Wan Y, Sun Y, Li Z, Lu H. Polym Chem, 2016, 7(41):6375-6382 doi: 10.1039/C6PY01364C
1. [1]
  Ruiying WANG , Hui WANG , Fenglan CHAI , Zhinan ZUO , Benlai WU . Three-dimensional homochiral Eu(Ⅲ) coordination polymer and its amino acid configuration recognition. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 877-884. doi: 10.11862/CJIC.20250052
2. [2]
  Xinyi Hong , Tailing Xue , Zhou Xu , Enrong Xie , Mingkai Wu , Qingqing Wang , Lina Wu . Non-Site-Specific Fluorescent Labeling of Proteins as a Chemical Biology Experiment. University Chemistry, 2024, 39(4): 351-360. doi: 10.3866/PKU.DXHX202310010
3. [3]
  Shuwen SUN , Gaofeng WANG . Two cadmium coordination polymers constructed by varying Ⅴ-shaped co-ligands: Syntheses, structures, and fluorescence properties. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 613-620. doi: 10.11862/CJIC.20230368
4. [4]
  Gaofeng WANG , Shuwen SUN , Yanfei ZHAO , Lixin MENG , Bohui WEI . Structural diversity and luminescence properties of three zinc coordination polymers based on bis(4-(1H-imidazol-1-yl)phenyl)methanone. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 849-856. doi: 10.11862/CJIC.20230479
5. [5]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
6. [6]
  Runjie Li , Hang Liu , Xisheng Wang , Wanqun Zhang , Wanqun Hu , Kaiping Yang , Qiang Zhou , Si Liu , Pingping Zhu , Wei Shao . 氨基酸的衍生及手性气相色谱分离创新实验. University Chemistry, 2025, 40(6): 286-295. doi: 10.12461/PKU.DXHX202407059
7. [7]
  Hong CAI , Jiewen WU , Jingyun LI , Lixian CHEN , Siqi XIAO , Dan LI . Synthesis of a zinc-cobalt bimetallic adenine metal-organic framework for the recognition of sulfur-containing amino acids. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 114-122. doi: 10.11862/CJIC.20240382
8. [8]
  Yaping Li , Sai An , Aiqing Cao , Shilong Li , Ming Lei . The Application of Molecular Simulation Software in Structural Chemistry Education: First-Principles Calculation of NiFe Layered Double Hydroxide. University Chemistry, 2025, 40(3): 160-170. doi: 10.12461/PKU.DXHX202405185
9. [9]
  Qiaowen CHANG , Ke ZHANG , Guangying HUANG , Nuonan LI , Weiping LIU , Fuquan BAI , Caixian YAN , Yangyang FENG , Chuan ZUO . Syntheses, structures, and photo-physical properties of iridium phosphorescent complexes with phenylpyridine derivatives bearing different substituting groups. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 235-244. doi: 10.11862/CJIC.20240311
10. [10]
  Yongjie ZHANG , Bintong HUANG , Yueming ZHAI . Research progress of formation mechanism and characterization techniques of protein corona on the surface of nanoparticles. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2318-2334. doi: 10.11862/CJIC.20240247
11. [11]
  Zeyu XU , Anlei DANG , Bihua DENG , Xiaoxin ZUO , Yu LU , Ping YANG , Wenzhu YIN . Evaluation of the efficacy of graphene oxide quantum dots as an ovalbumin delivery platform and adjuvant for immune enhancement. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1065-1078. doi: 10.11862/CJIC.20240099
12. [12]
  Zongfei YANG , Xiaosen ZHAO , Jing LI , Wenchang ZHUANG . Research advances in heteropolyoxoniobates. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 465-480. doi: 10.11862/CJIC.20230306
13. [13]
  Keying Qu , Jie Li , Ziqiu Lai , Kai Chen . Unveiling the Mystery of Chirality from Tartaric Acid. University Chemistry, 2024, 39(9): 369-378. doi: 10.12461/PKU.DXHX202310091
14. [14]
  Haitang WANG , Yanni LING , Xiaqing MA , Yuxin CHEN , Rui ZHANG , Keyi WANG , Ying ZHANG , Wenmin WANG . Construction, crystal structures, and biological activities of two Ln^Ⅲ₃ complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1474-1482. doi: 10.11862/CJIC.20240188
15. [15]
  Ji Qi , Jianan Zhu , Yanxu Zhang , Jiahao Yang , Chunting Zhang . Visible Color Change of Copper (II) Complexes in Reversible SCSC Transformation: The Effect of Structure on Color. University Chemistry, 2024, 39(3): 43-57. doi: 10.3866/PKU.DXHX202307050
16. [16]
  Tianyun Chen , Ruilin Xiao , Xinsheng Gu , Yunyi Shao , Qiujun Lu . Synthesis, Crystal Structure, and Mechanoluminescence Properties of Lanthanide-Based Organometallic Complexes. University Chemistry, 2024, 39(5): 363-370. doi: 10.3866/PKU.DXHX202312017
17. [17]
  Yuxin CHEN , Yanni LING , Yuqing YAO , Keyi WANG , Linna LI , Xin ZHANG , Qin WANG , Hongdao LI , Wenmin WANG . Construction, structures, and interaction with DNA of two Sm^Ⅲ₄ complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(6): 1141-1150. doi: 10.11862/CJIC.20240258
18. [18]
  Hong Zheng , Xin Peng , Chunwang Yi . The Tale of Caprolactam Cyclic Oligomers: The Ever-changing Life of “Princess Cyclo”. University Chemistry, 2024, 39(9): 40-47. doi: 10.12461/PKU.DXHX202403058
19. [19]
  Baitong Wei , Jinxin Guo , Xigong Liu , Rongxiu Zhu , Lei Liu . Theoretical Study on the Structure, Stability of Hydrocarbon Free Radicals and Selectivity of Alkane Chlorination Reaction. University Chemistry, 2025, 40(3): 402-407. doi: 10.12461/PKU.DXHX202406003
20. [20]
  Xilin Zhao , Xingyu Tu , Zongxuan Li , Rui Dong , Bo Jiang , Zhiwei Miao . Research Progress in Enantioselective Synthesis of Axial Chiral Compounds. University Chemistry, 2024, 39(11): 158-173. doi: 10.12461/PKU.DXHX202403106

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(108)
HTML views(7)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142