title: Antimicrobial activity and stability of the D-amino acid substituted derivatives of antimicrobial peptide polybia-MPI.
abstract: 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 α-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 α-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.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The People's Hospital in Gansu Province, 204 West Donggang Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Peng
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Zhu
authors.affiliation: The People's Hospital in Gansu Province, 204 West Donggang Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Wang
authors.affiliation: The People's Hospital in Gansu Province, 204 West Donggang Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China. wangkr@lzu.edu.cn.
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China. yanwj@lzu.edu.cn.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yan
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, People's Republic of China. wangrui@lzu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
keywords: Antimicrobial peptide; D-Amino acid substitution; Polybia-MPI; Stability