English
新闻公告
More
化学进展 DOI: 10.7536/PC171125 前一篇   后一篇

• 综述 •

抗菌肽及类抗菌肽的设计、合成及应用

周欣宇, 周春才*   

  1. 同济大学材料科学与工程学院 上海 201804
  • 收稿日期:2017-11-21 修回日期:2018-01-05 出版日期:2018-07-15 发布日期:2018-04-09
  • 通讯作者: 周春才 E-mail:cczhou@tongji.edu.cn
  • 基金资助:
    国家自然科学基金项目(No.51773153,21274110)资助

Design, Synthesis and Applications of Antimicrobial Peptides and Antimicrobial Peptide-Mimetic Copolymers

Chuncai Zhou, Chuncai Zhou*   

  1. School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
  • Received:2017-11-21 Revised:2018-01-05 Online:2018-07-15 Published:2018-04-09
  • Supported by:
    The work was supported by the National Natural Science Foundation of China(No. 51773153, 21274110).
抗菌肽是大多数生物体中均存在的阳离子型短肽,其构成了生物免疫系统的重要部分。抗菌肽具有广谱高效的抗菌性和细胞选择性,其独特的膜破坏杀菌机制不易引起病原体的耐药性突变,有望成为新一代控制病原体的有效"抗生素"。但天然抗菌肽的提取成本高、产率低且周期长,不利于大规模生产推广,所以依托化学合成方法合成抗菌肽及其模拟聚合物应运而生。该方法为抗菌肽的设计及合成提供无限可能。本文介绍了抗菌肽的来源、结构和其作用机理并对现有的抗菌肽合成方法进行综述,阐述了现今抗菌肽及类抗菌肽的研究进展以及抗菌肽组装体的应用,最后对抗菌肽及类抗菌肽的发展前景作了展望,为开发高效、低毒的"新一代"抗生素提供重要信息和策略。
Antibiotics resistance of bacteria has caused serious threats to public health and it is urgent to develop novel antibacterial agents that do not induce drug-resistance. Antimicrobial peptides(AMPs), constituting important parts of the immune system, are cationic short peptides produced by most living creatures such as bacteria, plants, fish, insects, mammal animals and so on. AMPs possess many excellent properties, including broad-spectrum antibacterial efficacy, high selectivity and unique membrane-destruction bactericidal mechanism. Thus, AMPs have become a promising candidate to overcome superbugs. However, over-costing and time-consuming production of natural AMPs limit their large-scale application. Therefore, low-cost and convenient synthesis methods have emerged, such as liquid-phase synthesis, solid-phase synthesis and N-carboxyanhydrides(NCA) ring-opening polymerization. Meanwhile, novel peptide-mimetic antibacterial polymers provide unlimited possibilities for development of peptide-based antibacterial agents and broaden their application fields. In this review, the sources, structure and antibacterial mechanism of AMPs are introduced. The synthesis methods to date of AMPs are also reviewed. Moreover, the development of antimicrobial peptide-mimetic copolymers and application of their assemblies are summarized as well. Finally, the shortcomings and the further development of antimicrobial peptides are discussed, providing advice for development of efficient, low toxicity "new generation antibiotic" in the future.
Contents
1 Introduction
2 Antimicrobial peptides
2.1 Source of antimicrobial peptides
2.2 Structure of antimicrobial peptides
2.3 Antibacterial mechanism of antimicrobial peptides
2.4 Synthesis of antimicrobial peptides
3 Antimicrobial peptide-mimetic copolymers
4 Antimicrobial nanoparticles
5 Conclusion and outlook

中图分类号: 

()
[1] Singh S B, Young K, Silver L L. Biochem. Pharmacol., 2017, 133:63.
[2] Y?lmaz Ç, Özcengiz G. Biochem. Pharmacol., 2017, 133:43.
[3] Bechinger B, Gorr S U. J. Dent. Res., 2017, 96:254.
[4] Gelband H, Miller P M, Pant S, Gandra S, Levinson J, Barter D, White A, Laxminarayan R. Wound Healing Southern Africa, 2015, 8:30.
[5] Raphael E, Riley L W. Frontiers in Medicine, 2017, 4:183.
[6] Khoshnood S, Heidary M, Mirnejad R, Bahramian A, Sedighi M, Mirzaei H. Biomed. Pharmacother., 2017, 94:982.
[7] Neu H C. Science, 1992, 257:1064.
[8] Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher H W, Scheld W M, Bartlett J G, Edwards J J. Clin. Infect. Dis., 2008, 46:155.
[9] Talbot G H, Bradley J, Edwards J J E, Gilbert D, Scheld M, Bartlett J G. Clin. Infect. Dis., 2006, 42:657.
[10] Boman H G. Cell, 1991, 65:205.
[11] Hancock R E W, Diamond G. Trends Microbiol., 2000, 8:402.
[12] Hancock R E W, Sahl H G. Nat Biotech., 2006, 24:1551.
[13] Chen C, Chen Y, Yang C, Zeng P, Xu H, Pan F, Lu J R. ACS Appl. Mater. Interfaces, 2015, 7:17346.
[14] Reddy K V R, Yedery R D, Aranha C. Int. J. Antimicrob. Agents, 2004, 24:536.
[15] Zasloff M. Nature, 2002, 415:389.
[16] Brogden K A. Nat. Rev. Microbiol., 2005, 3:238.
[17] Delves-Broughton J, Blackburn P, Evans R J, Hugenholtz J. Antonie van Leeuwenhoek, 1996, 69:193.
[18] Jung D, Powers J P, Straus S K, Hancock R E W. Chem. Phys. Lipids, 2008, 154:120.
[19] Liu L, Xu K, Wang H, Jeremy T P K, Fan W, Venkatraman S S, Li L, Yang Y Y. Nat. Nanotechnol., 2009, 4:457.
[20] Zhou C, Wang M, Zou K, Chen J, Zhu Y, Du J. ACS Macro Lett., 2013, 2:1021.
[21] Carrasco L, VÁZquez D, HernÁNdez-Lucas C, Carbonero P, GarcÍA-Olmedo F. Eur. J. Biochem., 1981, 116:185.
[22] Bohlmann H, Broekaert W. Crit. Rev. Plant Sci., 1994, 13:1.
[23] Baroni A, Donnarumma G, Paoletti I, Longanesi-Cattani I, Bifulco K, Tufano M A, Carriero M V. Peptides, 2009, 30:267.
[24] Wang G. Pharmaceuticals, 2013, 6:728.
[25] Cleveland J, Montville T J, Nes I F, Chikindas M L. Int. J. Food Microbiol., 2001, 71:1.
[26] Ahmad V, Khan M S, Jamal Q M S, Alzohairy M A, Al Karaawi M A, Siddiqui M U. Int. J. Antimicrob. Agents., 2017, 49:1.
[27] Benko-Iseppon A M, Lins-Galdino S, Calsa T, Akio-Kido E, Tossi A, Carlos B L, Crovella S. Curr. Protein Pept. Sci., 2010, 11:181.
[28] Guzmán-Rodríguez J J, Ochoa-Zarzosa A, López-Gómez R, López-Meza J E. Biomed. Res. Int., 2015, 11.
[29] Ageitos J M, Sánchez-Pérez A, Calo-Mata P, Villa T G. Biochem. Pharmacol., 2017, 133:117.
[30] Brogden K A, Ackermann M, McCray P B, Tack B F. Int. J. Antimicrob. Agents, 2003, 22:465.
[31] Wang Z, Wang G. Nucleic Acids Res., 2004, 32:D590.
[32] Yount N Y, Bayer A S, Xiong Y Q, Yeaman M R. Pept. Sci., 2006, 84:435.
[33] Jenssen H, Hamill P, Hancock R E W. Clin. Microbiol. Rev., 2006, 19:491.
[34] Li Y, Xiang Q, Zhang Q, Huang Y, Su Z. Peptides, 2012, 37:207.
[35] Hallock K J, Lee D K, Ramamoorthy A. Biophys. J., 2003, 84:3052.
[36] Henzler W K A, Lee D K, Ramamoorthy A. Biochemistry, 2003, 42:6545.
[37] Matsuzaki K, Murase O, Fujii N, Miyajima K. Biochemistry, 1996, 35:11361.
[38] Yang L, Harroun T A, Weiss T M, Ding L, Huang H W. Biophys. J., 2001, 81:1475.
[39] Zhang L, Rozek A, Hancock R E W. J. Biol. Chem., 2001, 276:35714.
[40] Powers J P S, Tan A, Ramamoorthy A, Hancock R E W. Biochemistry, 2005, 44:15504.
[41] Wu M, Maier E, Benz R, Hancock R E W. Biochemistry, 1999, 38:7235.
[42] Nakamura T, Furunaka H, Miyata T, Tokunaga F, Muta T, Iwanaga S, Niwa M, Takao T, Shimonishi Y. J. Biol. Chem., 1988, 263:16709.
[43] Diamond G, Zasloff M, Eck H, Brasseur M, Maloy W L, Bevins C L. Proc. Natl. Acad. Sci. U. S. A., 1991, 88:3952.
[44] Miyata T, Tokunaga F, Yoneya T, Yoshikawa K, Iwanaga S, Niwa M, Takao T, Shimonishi Y. J. Biochem., 1989, 106:663.
[45] Shafer W M, Martin L E, Spitznagel J K. Infect. Immun., 1984, 45:29.
[46] Sasaki Y, Coy D H. Peptides, 1987, 8:119.
[47] Merrifield R B. Adv. Enzymol. Relat. Areas Mol. Biol., 1969, 32:221.
[48] Haynes S R, Hagins S D, Juban M M, Elzer P H, Hammer R P. J. Pept. Res., 2005, 66:333.
[49] Ng-Choi I, Soler M, Cerezo V, Badosa E, Montesinos E, Planas M, Feliu L. Eur. J. Org. Chem., 2012, 4321.
[50] Andreu D, Merrifield R B, Steiner H, Boman H G. Proc. Natl. Acad. Sci. U. S. A., 1983, 80:6475.
[51] Pellois J P, Wang W, Gao X. J. Comb. Chem., 2000, 2:355.
[52] Fields G B, Noble R L. Int. J. Pept. Protein Res., 1990, 35:161.
[53] Wenschuh H, Beyermann M, Haber H, Seydel J K, Krause E, Bienert M, Carpino L A, El-Faham A, Albericio F. J. Org. Chem., 1995, 60:405.
[54] Pantarotto D, Bianco A, Pellarini F, Tossi A, Giangaspero A, Zelezetsky I, Briand J P, Prato M. J. Am. Chem. Soc., 2002, 124:12543.
[55] King D S, Fields C G, Fields G B. Int. J. Pept. Protein Res., 1990, 36:255.
[56] Woodward R B, Schramm C H. J. Am. Chem. Soc., 1947, 69:1551.
[57] Aliferis T, Iatrou H, Hadjichristidis N. Biomacromolecules, 2004, 5:1653.
[58] Zhou C, Qi X, Li P, Chen W N, Mouad L, Chang M W, Leong S S J, Chan-Park M B. Biomacromolecules, 2010, 11:60.
[59] Su X, Zhou X, Tan Z, Zhou C. Biopolymers, 2017, 107:e23041.
[60] Li P, Zhou C, Rayatpisheh S, Ye K, Poon Y F, Hammond P T, Duan H, Chan-Park M B. Adv. Mater., 2012, 24:4130.
[61] Wade D, Boman A, Wåhlin B, Drain C M, Andreu D, Boman H G, Merrifield R B. Proc. Natl. Acad. Sci. U. S. A., 1990, 87:4761.
[62] Shai Y. Pept. Sci., 2002, 66:236.
[63] Oren Z, Ramesh J, Avrahami D, Suryaprakash N, Shai Y, Jelinek R. Eur. J. Biochem., 2002, 269:3869.
[64] Zhou C, Yuan Y, Zhou P, Wang F, Hong Y, Wang N, Xu S, Du J. Biomacromolecules, 2017, 18:4154
[65] Lam S J, O'Brien-Simpson N M, Pantarat N, Sulistio A, Wong E H H, Chen Y Y, Lenzo J C, Holden J A, Blencowe A, Reynolds E C, Qiao G G. Nat. Microbiol., 2016, 1:16162.
[66] Yang X, Hu K, Hu G, Shi D, Jiang Y, Hui L, Zhu R, Xie Y, Yang L. Biomacromolecules, 2014, 15:3267.
[67] Kuroda K, DeGrado W F. J. Am. Chem. Soc., 2005, 127:4128.
[68] Punia A, He E, Lee K, Banerjee P, Yang N L. Chem. Commun., 2014, 50:7071.
[69] Michl T D, Locock K E S, Stevens N E, Hayball J D, Vasilev K, Postma A, Qu Y, Traven A, Haeussler M, Meagher L, Griesser H J. Polym. Chem., 2014, 5:5813.
[70] Choi H, Chakraborty S, Liu R, Gellman S H, Weisshaar J C. ACS Chem. Biol., 2016, 11:113.
[71] Hovakeemian S G, Liu R H, Gellman S H, Heerklotz H. Soft Matter, 2015, 11:6840.
[72] Mowery B P, Lee S E, Kissounko D A, Epand R F, Epand R M, Weisblum B, Stahl S S, Gellman S H. J. Am. Chem. Soc., 2007, 129:15474.
[73] Gabriel G J, Som A, Madkour A E, Eren T, Tew G N. Materials Science and Engineering:R:Reports, 2007, 57:28.
[74] Lienkamp K, Madkour A E, Musante A, Nelson C F, Nüsslein K, Tew G N. J. Am. Chem. Soc., 2008, 130:9836.
[75] Tew G N, Scott R W, Klein M L, DeGrado W F. Acc. Chem. Res., 2010, 43:30.
[76] Ilker M F, Nüsslein K, Tew G N, Coughlin E B. J. Am. Chem. Soc., 2004, 126:15870.
[77] Uppu D S S M, Samaddar S, Hoque J, Konai M M, Krishnamoorthy P, Shome B R, Haldar J. Biomacromolecules, 2016, 17:3094.
[78] Oda Y, Kanaoka S, Sato T, Aoshima S, Kuroda K. Biomacromolecules, 2011, 12:3581.
[79] Takahashi H, Caputo G A, Vemparala S, Kuroda K. Bioconjugate Chem., 2017, 28:1340.
[80] Chakraborty S, Liu R H, Hayouka Z, Chen X Y, Ehrhardt J, Lu Q, Burke E, Yang Y Q, Weisblum B, Wong G C L, Masters K S, Gellman S H. J. Am. Chem. Soc., 2014, 136:14530.
[81] Zhang S, Holmes T, Lockshin C, Rich A. Proc. Natl. Acad. Sci. U. S. A., 1993, 90:3334.
[82] Gao J, Wang M, Wang F, Du J. Biomacromolecules, 2016, 17:2080.
[83] Zhou C, Zhou X, Su X. RSC Adv., 2017, 7:39718.
[1] 闫楚璇, 李青璘, 巩正奇, 陈颖芝, 王鲁宁. 纳米有机半导体光催化剂[J]. 化学进展, 2021, 33(11): 1917-1934.
[2] 冯业娜, 刘书河, 张书博, 薛彤, 庄鸿麟, 冯岸超. 基于聚合诱导自组装制备二氧化硅/聚合物纳米复合材料[J]. 化学进展, 2021, 33(11): 1953-1963.
[3] 杨强强, 李川, 于淑娴, 范书华, 王月霞, 洪敏. 纳米载体在共负载siRNA及化疗药物对逆转肿瘤多药耐药性方面的应用[J]. 化学进展, 2021, 33(10): 1900-1916.
[4] 王子瑄, 王跃飞, 齐崴, 苏荣欣, 何志敏. DNA-多肽复合分子的设计、组装与应用[J]. 化学进展, 2020, 32(6): 687-697.
[5] 智康康, 杨鑫. 天然产物凝胶及其凝胶质[J]. 化学进展, 2019, 31(9): 1314-1328.
[6] 张浩, 刘静, 崔崑, 姜涛, 马志. 含胍基抗菌聚合物的合成及应用[J]. 化学进展, 2019, 31(5): 681-689.
[7] 林代武, 邢起国, 王跃飞, 齐崴, 苏荣欣, 何志敏. 多肽超分子手性自组装与应用[J]. 化学进展, 2019, 31(12): 1623-1636.
[8] 刘耀华, 刘育. 基于偶氮功能基的光控超分子组装[J]. 化学进展, 2019, 31(11): 1528-1539.
[9] 徐子悦, 张运昌, 林佳乐, 王辉, 张丹维, 黎占亭. 药物输送体系构筑中的超分子组装策略[J]. 化学进展, 2019, 31(11): 1540-1549.
[10] 郭家田, 卢玉超, 毕晨, 樊佳婷, 许国贺, 马晶军. 刺激响应型肽自组装及其应用[J]. 化学进展, 2019, 31(1): 83-93.
[11] 徐柳, 钱晨, 朱辰奇, 陈志鹏, 陈瑞*. 基于多肽的纳米药物递送系统的研究[J]. 化学进展, 2018, 30(9): 1341-1348.
[12] 王继乾*, 闫宏宇, 李洁, 张丽艳, 赵玉荣, 徐海*. 基于多肽自组装的人工金属酶[J]. 化学进展, 2018, 30(8): 1121-1132.
[13] 王雪, 陈中慧, 卿光焱*. 基于磷脂膜的界面相互作用研究[J]. 化学进展, 2018, 30(7): 888-901.
[14] 陈诚, 董志强, 陈昊文, 陈杨, 朱志刚, 施惟恒. 二维光子晶体[J]. 化学进展, 2018, 30(6): 775-784.
[15] 高玉霞, 梁云, 胡君, 巨勇. 基于天然小分子化合物的超分子手性自组装[J]. 化学进展, 2018, 30(6): 737-752.
阅读次数
全文


摘要