文献类型：期刊文献

英文题名：Intramolecular cyclization of the antimicrobial peptide Polybia-MPI with triazole stapling: influence on stability and bioactivity

作者：Liu, Beijun[1,2];Zhang, Wei[1];Gou, Sanhu[1];Huang, Haifeng[3];Yao, Jia[4];Yang, Zhibin[5];Liu, Hui[2];Zhong, Chao[2];Liu, Beiyin[6];Ni, Jingman[1,2];Wang, Rui[1]

第一作者：Liu, Beijun

通信作者：Ni, JM[1];Wang, R[1]

机构：[1]Lanzhou Univ, Key Lab Preclin Study New Drugs Gansu Prov, Sch Basic Med Sci, Lanzhou 730000, Peoples R China;[2]Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China;[3]Shaanxi Prov Peoples Hosp, Xian 710068, Shanxi, Peoples R China;[4]Lanzhou Univ, Hosp 1, 199 West Donggang Rd, Lanzhou 730000, Peoples R China;[5]Dali Univ, Key Lab Entomol Biopharmaceut R&D Yunnan Prov, Dali 671000, Peoples R China;[6]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Peoples R China

第一机构：Lanzhou Univ, Key Lab Preclin Study New Drugs Gansu Prov, Sch Basic Med Sci, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Key Lab Preclin Study New Drugs Gansu Prov, Sch Basic Med Sci, Lanzhou 730000, Peoples R China.

年份：2017

卷号：23

期号：11

起止页码：824

外文期刊名：JOURNAL OF PEPTIDE SCIENCE

收录：;Scopus(收录号：2-s2.0-85031503495);WOS:【SCI-EXPANDED(收录号:WOS:000417444200004)】；

基金：This study was supported by the grants from the National Natural Science Foundation of China (Nos. 81273355, 81273440, and 91213302), the Key National S&T Program of the Ministry of Science and Technology (2012ZX09504001-003), Program for Changjiang Scholars and Innovative Research Team in University (IRT1137), and the Natural Science Foundation of Gansu Province (145RJZA075).

语种：英文

外文关键词：antimicrobial peptides; intramolecular cyclization; click chemistry; stability; antimicrobial activity; secondary structure; mechanism of action

摘要：Cationic antimicrobial peptides have attracted increasing attention as a novel class of antibiotics to treat infectious diseases caused by pathogenic bacteria. However, susceptibility to protease is a shortcoming in their development. Cyclization is one approach to increase the proteolytic resistance of peptides. Therefore, to improve the proteolytic resistance of Polybia-MPI, we have synthesized the MPI cyclic analogs C-MPI-1 (i-to-i+4) and C-MPI-2 (i-to-i+6) by copper(I)-catalyzed azide-alkyne cycloaddition. Compared with MPI, C-MPI-1 displayed sustained antimicrobial activity and had enhanced anti-trypsin resistance, while C-MPI-2 displayed no antimicrobial activity. The relationship between peptide structure and bioactivity was further investigated by probing the secondary structure of the peptides by circular dichroism. This showed that C-MPI-1 adopted an a-helical structure in aqueous solution and, interestingly, had increased a-helical conformation in 30 mM sodium dodecyl sulfate and 50% trifluoroethyl alcohol compared with MPI. C-MPI-2 that was not a-helical in structure, suggesting that the propensity for a-helix conformation may play an important role in cyclic peptide design. In addition, scanning electron microscopy, propidium iodide uptake, and membrane permeabilization assays indicated that MPI and the optimized analog C-MPI-1 had membrane-active action modes, indicating that the peptides would not be susceptible to conventional resistance mechanisms. Our study provides additional insight into the influence of intramolecular cyclization at various positions on peptide structure and biological activity. In conclusion, the design and synthesis of cyclic analogs via click chemistry offer a new strategy for the development of stable antimicrobial agents. Copyright (C) 2017 European Peptide Society and John Wiley & Sons, Ltd.