高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (4): 681-687.doi: 10.7503/cjcu20170596

• 有机化学 • 上一篇    下一篇

碱性氨基酸对螺旋型抗菌肽生物活性的影响

赵文采, 韩丽丽, 彭颖君, 王晓静, 刘晟宇, 李鹏飞, 黄宜兵(), 陈育新   

  1. 吉林大学分子酶学工程教育部重点实验室, 生命科学学院, 长春 130021
  • 收稿日期:2017-09-01 出版日期:2018-04-10 发布日期:2018-03-26
  • 作者简介:联系人简介: 黄宜兵, 男, 博士, 副教授, 主要从事多肽药物方面的研究. E-mail:huangyibing@jlu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号: 81373455)、 吉林省自然科学基金(批准号: 20180101250JC)和超分子结构与材料国家重点实验室开放课题(批准号: SKLSSM201708)资助

Effect of Basic Amino Acids on the Biological Activity of Helical Antimicrobial Peptide

ZHAO Wencai, HAN Lili, PENG Yingjun, WANG Xiaojing, LIU Shengyu, LI Pengfei, HUANG Yibing*(), CHEN Yuxin   

  1. Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education,School of Life Science, Jilin University, Changchun 130012, China
  • Received:2017-09-01 Online:2018-04-10 Published:2018-03-26
  • Contact: HUANG Yibing E-mail:huangyibing@jlu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.81373445), the Natural Science Foundation of Jilin Province, China(No.20180101250JC) and the Open Project of State Key Laboratory of Supramolecular Structure and Materials, China(No.SKLSSM201708)

摘要:

以螺旋型抗菌肽HPRP-A1为模板, 利用精氨酸(R)对HPRP-A1序列中的赖氨酸(K)进行不同位点、 不同数量的取代, 结合改造前后抗菌肽的螺旋度、 疏水性及自聚集常数等理化性质, 研究了螺旋型抗菌肽结构与活性的相关性. 进一步结合脂质体模拟和细胞膜穿透实验, 对螺旋型抗菌肽与不同类型细胞膜的相互作用过程进行了研究. 结果表明, 增加精氨酸的取代数量, 会增强抗菌肽的疏水性和螺旋度, 导致螺旋型抗菌肽对真核细胞的毒性增强; 但精氨酸的增加会伴随着抗菌肽自聚集能力的降低以及抗菌肽对细菌细胞膜的渗透性降低, 导致抗菌肽的抗菌活性降低. 本研究对于设计和改造具有应用前景的螺旋型抗菌肽具有重要指导意义.

关键词: 抗菌肽, 精氨酸, 赖氨酸, 脂质体模拟膜

Abstract:

In order to investigate the effect of basic amino acids on the biological activity of antimicrobial peptides, an α helical antimicrobial peptides of HPRP-A1 was used to design several peptide derivatives with different K/R ratio by substitution lysine(K) with arginine(R). The relationship between the structure and activity of helical antimicrobial peptides was studied by combining the biophysical properties such as helicity, hydrophobicity and peptide association parameter of antimicrobial peptides. The interaction between helical antimicrobial peptides and different types of cell membranes was further studied by liposome mimic membrane and the cell permeation ability of peptide was examined by 1-N-pbenyl-naphtylamine(NPN) and o-nitrophenyl-β-D-galactopyranoside(ONPG). The results confirmed that the increasing numbers of arginine substitution increased the hydrophobicity and helicity of the antimicrobial peptides, resulting in increasing toxicity of the helical antimicrobial peptides against eukaryotic cell membrane. However, the increasing of arginine was accompanied by decreasing in the ability of peptide association and the permeability of the antimicrobial peptide against the prokaryotic cell membrane, resulting in decreasing of the antibacterial activity of the antimicrobial peptide.

Key words: Antimicrobial peptide, Arginin, Lysine, Liposome mimic membrane

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