Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery

doi:10.1007/s40242-019-0060-z

Chemical Research in Chinese Universities ›› 2020, Vol. 36 ›› Issue (1): 134-138.doi: 10.1007/s40242-019-0060-z

• Articles • Previous Articles Next Articles

Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery

WANG Ruijue, SHENG Kai, HOU Yingqin, SUN Jialing, LU Hua

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

Received:2019-11-22 Revised:2019-12-18 Online:2020-02-01 Published:2019-12-18
Contact: LU Hua E-mail:chemhualu@pku.edu.cn
Supported by:
Supported by the National Key Research and Development Program of China(No.2016YFA0201400) and the National Natural Science Foundation of China(Nos.21434008, 21722401).

Abstract

Abstract: Protein delivery is of central importance for both diagnostic and therapeutic applications. However, protein delivery faces challenges including poor endosomal escape and thus limited efficiency. Here, we report the facile construction and screening of a small library of cationic helical polypeptides for cytosolic protein delivery. The library is based on a random copolymer poly(γ-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}esteryl-L-glutamate)-randompoly(γ-6-chlorohexyl-L-glutamate)[P(EG₃-r-ClC₆)Glu], which is then modified with various pyridine derivatives and alkyl thiols. Flow Cytometry, confocal laser scanning microscopy, and viability assay collaboratively identify two leading polymers, showing efficient delivery of enhanced green fluorescent protein(eGFP) and low cytoto-xicity. This finding is further validated by the cytosolic delivery of RNase A and cytochrome C(Cyt C) to HeLa cells in the viability assay. Together, this work demonstrates that high-throughput screening is an effective and viable approach to the selection of cationic helical polypeptides for the cytosolic delivery of functional proteins.

Key words: Cationic helical polypeptide, Protein delivery, Cytosolic protein

WANG Ruijue, SHENG Kai, HOU Yingqin, SUN Jialing, LU Hua. Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery[J]. Chemical Research in Chinese Universities, 2020, 36(1): 134-138.

References 49

[1]	Leader B., Baca Q. J., Golan D. E., Nat. Rev. Drug Discovery, 2008, 7, 21
[2]	Ray M., Lee Y. W., Scaletti F., Yu R. J., Rotello V. M., Nanomedicine, 2017, 12, 941
[3]	Liu X., Wu F., Ji Y., Yin L., Bioconjug. Chem., 2019, 30, 305
[4]	Lv J., Fan Q. Q., Wang H., Cheng Y., Biomaterials, 2019, 218, 119358
[5]	Yang X. T., Tang Q., Jiang Y., Zhang M., Wang M., Mao L. Q., J. Am. Chem. Soc., 2019, 141, 3782
[6]	Fu A., Tang R., Hardie J., Farkas E. M., Rotello M. V., Bioconjug. Chem., 2014, 25, 1602
[7]	Qin X., Yu C., Wei J., Li L., Zhang C., Wu Q., Huang W., Adv. Mater., 2019, 31, 1902791
[8]	Gu Z., Biswas A., Zhao M., Tang Y., Chem. Soc. Rev., 2011, 40, 3638
[9]	Dahan R., Barnhart C. B., Li F., Yamniuk P. A., Korman J. A., Ravetch V. J., Cancer Cell, 2016, 29, 820
[10]	Leonard W. J., Lin J. X., O'Shea J., Immunity, 2019, 50(4), 832
[11]	Simeon R. L., Chamoun A. M., McMillin T., Chen Z., ACS Chem. Biol., 2013, 8(12), 2678
[12]	McNaughton B. R., Cronican J. J., Thompson D. B., Proc. Natl. Acad. Sci. USA, 2009, 106(15), 6111
[13]	Mueller J., Kretzschmar I., Volkmer R., Boisguerin P., Bioconjug. Chem., 2008, 19, 2363
[14]	Futaki S., Nakase I., Acc. Chem. Res., 2017, 50(10), 2449
[15]	Zuris J. A., Thompson D. B., Shu Y., Guilinger J. P., Bessen J. L., Hu J. H., Maeder M. L., Joung J. K., Chen Z., Liu R., Nat. Biotechnol., 2015, 33, 73
[16]	Kim Y. B., Zhao K. T., Thompson D. B., Liu D. R., Nat. Commun., 2019, 10(1), 2905
[17]	Zhang P., Steinborn B., Lachelt U., Zahler S., Wagner E., Biomacromolecules, 2017, 18, 2509
[18]	Wang M., Sun S., Neufeld C. I., Perez-Ramirez B., Xu Q., Angew. Chem. Int. Ed., 2014, 53, 13444
[19]	Dutta K., Hu D., Zhao B., Ribbe A. E., Zhuang J. M., Thayumanavan S., J. Am. Chem. Soc., 2017, 139, 5676
[20]	Jian Y. Y., Lu H. X., Chen F., Callari M., Pourgholami M., Morris D. L., Stenzel M. H., Biomacromolecules, 2016, 17, 808
[21]	Su S., Wang Y. Y., Du F. S., Lu H., Li Z. C., Adv. Funct. Mater., 2018, 28, 1805287
[22]	Yan M., Du J., Gu Z., Gu Z., Liang M., Hu Y., Zhang W., Priceman S., Wu L., Zhou H., Liu Z., Segura T., Tang Y., Lu Y., Nat. Nanotech., 2010, 5, 48
[23]	Kuan S. L., Ng D. Y., Wu Y., Fortsch C., Barth H., Doroshenko M., Koynov K., Meier C., Weil T., J. Am. Chem. Soc., 2013, 135, 17254
[24]	Zhang J., Wu L., Meng F., Wang Z., Deng C., Liu H., Zhong Z., Langmuir, 2012, 28, 2056
[25]	Ding L., Jiang Y., Zhang J., Klok H. A., Zhong Z., Biomacromole-cules, 2018, 19, 555
[26]	He H., Chen Y., Li Y., Song Z., Zhong Y., Zhu R., Cheng J., Yin L., Adv. Funct. Mater., 2018, 28, 1706710
[27]	Lee Y., Lshii T., Kim H., Nishiyama N., Hayakawa Y., Itaka K., Kataoka K., Angew. Chem. Int. Ed., 2010, 122, 2606
[28]	Yu C., Tan E., Xu Y., Lv J., Cheng Y., Bioconjugate Chem., 2019, 30(2), 413
[29]	Xu J., Wang H., Xu L., Chao Y., Wang C., Han X., Dong Z., Chang H., Lv J., Gao X., Wang X., Wang H., Chen H., He X., Li L., Cheng Y., Nano Lett., 2017, 17, 1678
[30]	Liu C., Shen W., Li B., Li T., Chang H., Cheng Y., Chem. Mater., 2019, 31, 1956
[31]	Prior T. I., Fitzgerald D. J., Pastan I., Biochemistry, 1992, 31, 3555
[32]	Prior T. I., Fitzgerald D. J., Pastan I., Cell, 1991, 64, 1017
[33]	Rizk S. S., Luchniak A., Uysal S., Brawley C. M., Rock R. S., Kossiakoff A. A., Proc. Natl. Acad. Sci. USA, 2009, 106(27), 11011
[34]	Zhang Z., Shen W., Ling J., Yan Y., Hu J., Cheng Y., Nat. Commun., 2018, 9, 1377
[35]	Li G., Lei Q., Wang F., Deng D., Wang S., Tian L., Wu S., Cheng Y., Liu Z., Small, 2019, 15, 1900936
[36]	Lv J., He B., Yu J., Wang Y., Wang C., Zhang S., Wang H., Hu J., Zhang Q., Cheng Y., Biomaterials, 2018, 182, 167
[37]	Li G., Yuan S., Deng D., Ou T., Li Y., Sun R., Cheng Y., Liu Z., Adv. Funct. Mater., 2019, 29, 1901932
[38]	Liu C., Wang T., Wang H., Zhang S., Ping Y., Cheng Y., Science Advances, 2019, 5, eaaw8922
[39]	Panganiban B., Qiao B., Jiang T., Delre C., Obadia M. M., Nguyen T. D., Smith A. A. A., Hall A., Sit I., Crosby M. G., Dennis P. B., Drockenmuller E., Olvera M., Xu T., Science, 2018, 359(6381), 1239
[40]	Song Z., Zheng N., Ba X., Yin L., Zhang R., Ma L., Cheng J., Biomacromolecules, 2014, 15, 1491
[41]	Gabrielson N. P., Lu H., Yin L., Li D., Wang F., Cheng J., Angew. Chem. Int. Ed., 2012, 51, 1143
[42]	Yin L., Song Z., KimH. K., Zheng N., Tang H., Lu H., Gabrielson N. P., Cheng J., Biomaterials, 2013, 34, 2340
[43]	Zhang R., Zheng N., Song Z., Yin L., Cheng J., Biomaterials, 2014, 35, 3443
[44]	Zhang R., Song Z., Yin L., Lu H., Gabrielson N. P., Cheng J., WIREs Nanomedicine & Nanobiotechnology, 2015, 7, 98
[45]	Hou Y., Zhou Y., Wang H., Sun J., Wang R., Sheng K., Yuan J., Hu Y., Chao Y., Liu Z., Lu H., ACS Cent. Sci., 2019, 5, 229
[46]	Hou Y., Zhou Y., Wang H., Sun J., Wang R., Sheng K., Feng J., Yang S., Lu H., J. Am. Chem. Soc., 2018, 140, 1170
[47]	Lu H., Wang J., Bai Y., Lang J. W., Liu S., Lin Y., Cheng J., Nat. Commun., 2011, 2, 206
[48]	Ornelas-Megiatto C., Wich P. R., Fréchet J. M. J., J. Am. Chem. Soc., 2012, 134, 1902
[49]	LaRochelle J. R., Cobb G. B., Steinauer A., Rhoades E., Schepartz A., J. Am. Chem. Soc., 2015, 137, 2536

Tailoring Cationic Helical Polypeptides for Efficient Cytosolic Protein Delivery

Knowledge

Abstract

Cite this article

share this article

References 49

Related Articles 0

Recommended Articles

Metrics

Comments