Clickable, Oxidation-Responsive and Enzyme-DegradablePolypeptide: Synthesis, Characterization and Side Chain Modification

Yan-Zhi Lu; An-Qi Gu; Tian-Lun Shen; Ji-Hong Sun; Jun Ling

doi:10.1007/s10118-022-2745-x

Your Location：

Home >

Browse articles >

Clickable, Oxidation-Responsive and Enzyme-DegradablePolypeptide: Synthesis, Characterization and Side Chain Modification

RESEARCH ARTICLE | Updated：2022-10-25

- Clickable, Oxidation-Responsive and Enzyme-DegradablePolypeptide: Synthesis, Characterization and Side Chain Modification
- Clickable, Oxidation-Responsive and Enzyme-DegradablePolypeptide: Synthesis, Characterization and Side Chain Modification
- 高分子科学（英文版） 2022年40卷第11期页码：1360-1368
- Affiliations：
  
  a.Ministry of Education Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
  b.Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
- Author bio：
  
  lingjun@zju.edu.cn
- Funds：
  
  This work was financially supported by the Key Research and Development Program of Zhejiang Province (No. 2019C03014) and the National Natural Science Foundation of China (No. 21871232).
- DOI：10.1007/s10118-022-2745-x
  中图分类号：
- 收稿：2022-03-04，
  
  修回：2022-3-28，
  
  录用：2022-3-29，
  
  网络首发：2022-06-17，
  
  纸质出版：2022-11-01
- Accepted：
Scan QR Code
Lu, Y. Z.; Gu, A. Q.; Shen, T. L.; Sun, J. H.; Ling, J. Clickable, oxidation-responsive and enzyme-degradable polypeptide: synthesis, characterization and side chain modification. Chinese J. Polym. Sci. 2022, 40, 1360–1368

Yan-Zhi Lu, An-Qi Gu, Tian-Lun Shen, et al. Clickable, Oxidation-Responsive and Enzyme-DegradablePolypeptide: Synthesis, Characterization and Side Chain Modification[J]. Chinese Journal of Polymer Science, 2022, 40(11): 1360-1368.
Lu, Y. Z.; Gu, A. Q.; Shen, T. L.; Sun, J. H.; Ling, J. Clickable, oxidation-responsive and enzyme-degradable polypeptide: synthesis, characterization and side chain modification. Chinese J. Polym. Sci. 2022, 40, 1360–1368 DOI： 10.1007/s10118-022-2745-x.

Yan-Zhi Lu, An-Qi Gu, Tian-Lun Shen, et al. Clickable, Oxidation-Responsive and Enzyme-DegradablePolypeptide: Synthesis, Characterization and Side Chain Modification[J]. Chinese Journal of Polymer Science, 2022, 40(11): 1360-1368. DOI： 10.1007/s10118-022-2745-x.

摘要

Poly(

-allylcysteine)

PAC

was synthesized via NCA and NPC. PAC can be modified by thiol-ene functionalization of pendent unsaturated bonds and oxidation of thioether to sulfoxide. Polyalliin

the oxidation product of PAC

are enzymatically degradable.

Abstract

Modifications at polypeptide side chains have been found to affect conformational and properties

which is a vital strategy to prepare functional polypeptides. This contribution describes the synthesis of homo and co-polypeptides containing unsaturated bonds and thioether moieties

poly(

-allylcysteine) (PAC). The pendant vinyl groups provide an active binding site which are able to be further modified with cysteine by thiol-ene click reaction. The sulfoxide from thioether oxidation bestows the polypeptide water solubility and enzymatic catalytic sites. The self-assembly micelles of PEG-

-PAC are ruptured along with oxidation to release the Nile red payloads. Moreover

poly(

-allyl-cysteine sulfoxide)

aka

. polyalliin

is the oxidation product of PAC which undergoes side chain cleavage catalyzed by alliinase enzyme. The polypeptides are biocompatible as confirmed by cell viability assays and may find applications in drug delivery

biosensing and nanoreactor.

关键词

Keywords

references

Hu, J. J.; He, P. Y.; Li, Y. M . Chemical modifications of tryptophan residues in peptides and proteins . J. Pept. Sci. , 2021 . 27 e3286 .

Liu, X.; Sun, J.; Gao, W . Site-selective protein modification with polymers for advanced biomedical applications . Biomaterials , 2018 . 178 413 - 434 . DOI: 10.1016/j.biomaterials.2018.04.050 http://doi.org/10.1016/j.biomaterials.2018.04.050 .

Mozhdehi, D.; Luginbuhl, K. M.; Simon, J. R.; Dzuricky, M.; Berger, R.; Varol, H. S.; Huang, F. C.; Buehne, K. L.; Mayne, N. R.; Weitzhandler, I.; Bonn, M.; Parekh, S. H.; Chilkoti, A . Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly . Nat. Chem. , 2018 . 10 496 - 505 . DOI: 10.1038/s41557-018-0005-z http://doi.org/10.1038/s41557-018-0005-z .

Cao, J.; Hu, P.; Lu, L.; Chan, B . A.; Luo, B.; Zhang, D. Non-ionic water-soluble “clickable” α -helical polypeptides: synthesis, characterization and side chain modification . Polym. Chem. , 2015 . 6 1226 - 1229 . DOI: 10.1039/C4PY01560F http://doi.org/10.1039/C4PY01560F .

Deming, T. J . Synthesis of side-chain modified polypeptides . Chem. Rev. , 2016 . 116 786 - 808 . DOI: 10.1021/acs.chemrev.5b00292 http://doi.org/10.1021/acs.chemrev.5b00292 .

Deng, C.; Wu, J.; Cheng, R.; Meng, F.; Klok, H.; Zhong, Z . Functional polypeptide and hybrid materials: precision synthesis via α -amino acid N -carboxyanhydride polymerization and emerging biomedical applications . Prog. Polym. Sci. , 2014 . 39 330 - 364 . DOI: 10.1016/j.progpolymsci.2013.10.008 http://doi.org/10.1016/j.progpolymsci.2013.10.008 .

Xiao, J.; Tan, J.; Jiang, R.; He, X.; Xu, Y.; Ling, Y.; Luan, S.; Tang, H . A pH and redox dual responsive homopolypeptide: synthesis, characterization, and application in “smart” single-walled carbon nanotube dispersion . Polym. Chem. , 2017 . 8 7025 - 7032 . DOI: 10.1039/C7PY01393K http://doi.org/10.1039/C7PY01393K .

Gharakhanian, E. G.; Bahrun, E.; Deming, T. J . Influence of Sulfoxide group placement on polypeptide conformational stability . J. Am. Chem. Soc. , 2019 . 141 14530 - 14533 . DOI: 10.1021/jacs.9b07223 http://doi.org/10.1021/jacs.9b07223 .

Krannig, K. S.; Schlaad, H . pH-Responsive bioactive glycopolypeptides with enhanced helicity and solubility in aqueous solution . J. Am. Chem. Soc. , 2012 . 134 18542 - 18545 . DOI: 10.1021/ja308772d http://doi.org/10.1021/ja308772d .

Krannig, K . S.; Sun, J.; Schlaad, H. Stimuli-responsivity of secondary structures of glycopolypeptides derived from poly(L-glutamate- co -allylglycine) . Biomacromolecules , 2014 . 15 978 - 984 . DOI: 10.1021/bm401883p http://doi.org/10.1021/bm401883p .

Perlin, P.; Scott, W. A.; Deming, T. J . Modification of poly(5,6-epoxy- l -norleucine) gives functional polypeptides with alternative side-chain linkages . Biomacromolecules , 2020 . 21 126 - 132 . DOI: 10.1021/acs.biomac.9b01065 http://doi.org/10.1021/acs.biomac.9b01065 .

Xiao, Y.; Tang, C.; Chen, Y.; Lang, M . Dual stimuli-responsive polypeptide prepared by thiol-ene click reaction of poly(L-cysteine) and N,N -dimethylaminoethyl acrylate . Biopolymers , 2019 . 110 e23318 .

Zhou, J.; Chen, P.; Deng, C.; Meng, F.; Cheng, R.; Zhong, Z . A simple and versatile synthetic strategy to functional polypeptides via vinyl sulfone-substituted L-cysteine N-carboxyanhydride . Macromolecules , 2013 . 46 6723 - 6730 . DOI: 10.1021/ma4014669 http://doi.org/10.1021/ma4014669 .

Deng, Y.; Chen, H.; Tao, X.; Cao, F.; Trepout, S.; Ling, J.; Li, M. H . Oxidation-sensitive polymersomes based on amphiphilic diblock copolypeptoids . Biomacromolecules , 2019 . 20 3435 - 3444 . DOI: 10.1021/acs.biomac.9b00713 http://doi.org/10.1021/acs.biomac.9b00713 .

Yue, S.; Bai, T.; Xu, S.; Shen, T.; Ling, J.; Ni, X . Ring-opening polymerization of CO 2 -based disubstituted δ -valerolactone toward sustainable functional polyesters . ACS Macro Lett. , 2021 . 10 1055 - 1060 . DOI: 10.1021/acsmacrolett.1c00341 http://doi.org/10.1021/acsmacrolett.1c00341 .

Gangloff, N.; Ulbricht, J.; Lorson, T.; Schlaad, H.; Luxenhofer, R . Peptoids and polypeptoids at the frontier of supra- and macromolecular engineering . Chem. Rev. , 2016 . 116 1753 - 1802 . DOI: 10.1021/acs.chemrev.5b00201 http://doi.org/10.1021/acs.chemrev.5b00201 .

Lee, D.; Rejinold, N. S.; Jeong, S. D.; Kim, Y. C . Stimuli-responsive polypeptides for biomedical applications . Polymers , 2018 . 10 830 DOI: 10.3390/polym10080830 http://doi.org/10.3390/polym10080830 .

Sun, H.; Zhong, Z . 100 th Anniversary of macromolecular science viewpoint: biological stimuli-sensitive polymer prodrugs and nanoparticles for tumor-specific drug delivery . ACS Macro Lett. , 2020 . 9 1292 - 1302 . DOI: 10.1021/acsmacrolett.0c00488 http://doi.org/10.1021/acsmacrolett.0c00488 .

Tao, W.; He, Z . ROS-responsive drug delivery systems for biomedical applications . Asian J. Pharm. , 2018 . 13 101 - 112 . .

Zhang, T.; Yao, J.; Tian, J.; Deng, M.; Zhuang, X.; Xiao, C . Synthesis of polypeptide bearing 1,4-dithiane pendants for ROS-responsive drug release . Chin. Chem. Lett. , 2020 . 31 1129 - 1132 . DOI: 10.1016/j.cclet.2019.07.010 http://doi.org/10.1016/j.cclet.2019.07.010 .

Zhang, Y.; He, P; Liu, X.; Zhang, H.; Yang, H.; Xiao, C.; Chen, X . Synthesis of PEGylated alternating copolymer bearing thioether pendants for oxidation responsive drug delivery . Eur. Polym. J. , 2018 . 107 308 - 314 . DOI: 10.1016/j.eurpolymj.2018.09.004 http://doi.org/10.1016/j.eurpolymj.2018.09.004 .

Akbulut, H.; Yamada, S.; Endo, T . Phosgene-free synthesis of poly(L-cysteine) containing styrene moiety as a reactive function . Macromol. Chem. Phys. , 2017 . 218 1700078 DOI: 10.1002/macp.201700078 http://doi.org/10.1002/macp.201700078 .

Habraken, G. J.; Koning, C. E.; Heuts, J. P.; Heise, A . Thiol chemistry on well-defined synthetic polypeptides . Chem. Commun. , 2009 . 24 3612 - 3614 . .

Finkel, T . Signal transduction by reactive oxygen species . J. Cell Biol. , 2011 . 194 7 - 15 . DOI: 10.1083/jcb.201102095 http://doi.org/10.1083/jcb.201102095 .

Brosnan, S. M.; Schlaad, H . Modification of polypeptide materials by Thiol-X chemistry . Polymer , 2014 . 55 5511 - 5516 . DOI: 10.1016/j.polymer.2014.08.067 http://doi.org/10.1016/j.polymer.2014.08.067 .

Yamada, S.; Goto, M.; Endo, T . Convenient phosgene-free synthesis of polypeptides bearing reactive alkene moiety through polycondensation of activated urethane derivative of α -amino acid . Polymer , 2016 . 93 174 - 180 . DOI: 10.1016/j.polymer.2016.04.029 http://doi.org/10.1016/j.polymer.2016.04.029 .

Chen, Y.; Yu, L.; Zhang, B.; Feng, W.; Xu, M.; Gao, L.; Liu, N.; Wang, Q.; Huang, X.; Li, P.; Huang, W . Design and synthesis of biocompatible, hemocompatible, and highly selective antimicrobial cationic peptidopolysaccharides via Click chemistry . Biomacromolecules , 2019 . 20 2230 - 2240 . DOI: 10.1021/acs.biomac.9b00179 http://doi.org/10.1021/acs.biomac.9b00179 .

Su, Y.; Tian, L.; Yu, M.; Gao, Q.; Wang, D.; Xi, Y.; Yang, P.; Lei, B.; Ma, P. X.; Li, P . Cationic peptidopolysaccharides synthesized by ‘click’ chemistry with enhanced broad-spectrum antimicrobial activities . Polym. Chem. , 2017 . 8 3788 - 3800 . DOI: 10.1039/C7PY00528H http://doi.org/10.1039/C7PY00528H .

Robinson, J. W.; Schlaad, H . A versatile polypeptoid platform based on N -allyl glycine . Chem. Commun. , 2012 . 48 7835 - 7837 . DOI: 10.1039/c2cc33881e http://doi.org/10.1039/c2cc33881e .

Sun, J.; Schlaad, H . Thiol-ene clickable polypeptides . Macromolecules , 2010 . 43 4445 - 4448 . DOI: 10.1021/ma100401m http://doi.org/10.1021/ma100401m .

Tian, Z . Y.; Zhang, Z.; Wang, S.; Lu, H. A moisture-tolerant route to unprotected alpha/beta-amino acid N -carboxyanhydrides and facile synthesis of hyperbranched polypeptides . Nat. Commun. , 2021 . 12 5810 DOI: 10.1038/s41467-021-25689-y http://doi.org/10.1038/s41467-021-25689-y .

Doriti, A.; Brosnan, S. M.; Weidner ,S. M.; Schlaad, H . Synthesis of polysarcosine from air and moisture stable N -phenoxycarbonyl- N -methylglycine assisted by tertiary amine base . Polym. Chem. , 2016 . 7 3067 - 3070 . DOI: 10.1039/C6PY00221H http://doi.org/10.1039/C6PY00221H .

Kamei, Y.; Sudo, A.; Nishida, H.; Kikukawa, K.; Endo, T . Synthesis of polypeptides from activated urethane derivatives of α-amino acids . J. Polym. Sci., Part A: Polym. Chem. , 2008 . 46 2525 - 2535 . DOI: 10.1002/pola.22584 http://doi.org/10.1002/pola.22584 .

Yang, Z.; Bai, T.; Ling, J.; Shen, Y . Hydroxyl-tolerated polymerization of N -phenoxycarbonyl α -amino acids: a simple way to polypeptides bearing hydroxyl groups . J. Polym. Sci., Part A: Polym. Chem. , 2019 . 57 907 - 916 . DOI: 10.1002/pola.29343 http://doi.org/10.1002/pola.29343 .

Abdi, S. A. H.; Afjal, M. A.; Najmi, A. K.; Raisuddin, S . S -allyl cysteine ameliorates cyclophosphamide-induced downregulation of urothelial uroplakin IIIa with a concomitant effect on expression and release of CCL11 and TNF-alpha in mice . Pharmacol. Rep. , 2018 . 70 769 - 776 . DOI: 10.1016/j.pharep.2018.02.016 http://doi.org/10.1016/j.pharep.2018.02.016 .

Jan, B.; Frank, A.; Martin, C. H. G.; Ifeanyi, D. N.; Alan, J. S . Allicin: chemistry and biological properties . Molecules , 2014 . 19 12591 - 12618 . DOI: 10.3390/molecules190812591 http://doi.org/10.3390/molecules190812591 .

Miron, T.; Bercovici, T; Rabinkov, A.; Wilchek, M.; Mirelman, D . [3H]Allicin: preparation and applications . Anal. Biochem. , 2004 . 331 364 - 369 . DOI: 10.1016/j.ab.2004.03.054 http://doi.org/10.1016/j.ab.2004.03.054 .

Orozco-Morales, M.; Hernandez-Pedro, N.; Barrios-Bernal, P.; Arrieta, O.; Ruiz-Godoy, L. M.; Santamaría, A.; Colín-González, A. L . S -allyl cysteine induces cytotoxic effects on human NSCLC cell lines . J. Thorac. Oncol. , 2019 . 14 S1181 .

Roman; Kubec; Jan; Velíek; Marek; Doleal; Vladimír; Kubelka . Sulfur-containing volatiles arising by thermal degradation of alliin and deoxyalliin . J. Agric. Food Chem. , 1997 . 45 3580 - 3585 . DOI: 10.1021/jf970071q http://doi.org/10.1021/jf970071q .

Frankel, M.; Zilkha, A . Synthesis of poly- S -Allylcysteine (poly-deoxo-alliin) . Nature , 1955 . 175 1045 - 1046 . .

Bonnet-Delpon, R . A selective conversion of sulfide to sulfoxide in hexafluoro-2-propanol . Tetrahedron Lett. , 1998 . 39 3141 - 3144 . DOI: 10.1016/S0040-4039(98)00498-5 http://doi.org/10.1016/S0040-4039(98)00498-5 .

浏览量

133

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Multiple-Responsive Chiral Hydrogels from Helical Dendronized Poly(phenylacetylene)s

Silk Sericin-inspired Poly-β-homoserine for Protein Protection

Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy

Chemoselective Ring-opening Copolymerization of CO2-based Lactones towards Functional Polyesters

Upgrading Commercially Available Polyethylene to High-value Materials with Strong Mechanical Performance and Hydrophilicity by Blending with Ethylene/meta-Methoxystyrene Copolymers