Antimicrobial activity and stability of the D-amino acid substituted derivatives of antimicrobial peptide polybia-MPI

被引：91

作者：

Zhao, Yanyan ^{[1
]}

Zhang, Min ^{[2
]}

Qiu, Shuai ^{[1
]}

Wang, Jiayi ^{[1
]}

Peng, Jinxiu ^{[1
]}

Zhao, Ping ^{[1
]}

Zhu, Ranran ^{[1
]}

Wang, Hailin ^{[2
]}

Li, Yuan ^{[2
]}

Wang, Kairong ^{[1
]}

Yan, Wenjin ^{[1
]}

Wang, Rui ^{[1
]}

机构：

[1] Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 222 Tian Shui South Rd, Lanzhou 730000, Peoples R China

[2] Peoples Hosp Gansu Prov, 204 West Donggang Rd, Lanzhou 730000, Peoples R China

来源：

AMB Express | 2016年 / 6卷

基金：

中国国家自然科学基金;

关键词：

Antimicrobial peptide; Polybia-MPI; Stability; D-Amino acid substitution; HOST-DEFENSE PEPTIDES; MULTIDRUG-RESISTANT; MEMBRANE INTEGRITY; CATIONIC PEPTIDES; PAULISTA; CELLS; VENOM; SUSCEPTIBILITY; PROTEOLYSIS; MECHANISM;

D O I：

10.1186/s13568-016-0295-8

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Antimicrobial peptide has the potential to be developed as new kind of antimicrobial agents with novel action mechanism. However, the susceptibility to protease is a drawback for potential peptides to be clinical used. D-amino acid substitution can be one way to increase the proteolytic stability of peptides. In the present study, we synthesized the d-lysines substituted analog (d-lys-MPI) and the D-enantiomer of polybia-MPI (D-MPI) to improve the proteolytic resistance of polybia-MPI. Our results showed that, the stability of its D-amino acid partially substituted analog D-lys-MPI was increased. However, it lost antimicrobial activity at the tested concentration with the loss of a-helix content. As shown in the CD spectra, after substitution, the spectra of D-MPI is symmetrical to MPI, indicated it turned into left hand a-helical conformation. Excitingly, the stability of D-MPI toward the tested protease was improved greatly. Notably, the antimicrobial activity of D-MPI was comparable to its L-counterpart MPI, even improved. In addition, the hemolytic activity of D-MPI was lowered. This also indicated that the action target of antimicrobial peptide polybia-MPI was not chiral specific. So, D-MPI may offer a therapeutic strategy to defend the infection of microbes, considering its stability to protease and relatively lower cytotoxicity to human erythrocytes.

引用

页数：11

共 35 条

[31] Dual antifungal properties of cationic antimicrobial peptides polybia-MPI: Membrane integrity disruption and inhibition of biofilm formation [J].