科研之友
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摘要
Antimicrobial peptides (AMPs) with amphipathic beta-hairpin structures have been demonstrated to possess potent antimicrobial activities and great cell selectivities. However, our understanding of beta-hairpin antimicrobial peptides lags behind that of alpha-helices, mainly because it is difficult for short peptides to form robust beta-hairpin structures. Tryptophan zipper (trpzip) peptides are among the most stable beta-hairpin peptides known to fold spontaneously without requiring covalent disulfide constraint or metal binding. To develop model beta-hairpin AMPs with small size and remarkable stability, a series of amphiphilic linear peptides were designed based on the trpzip motif. The sequence of designed peptides is (WK) (n) (D) PG(KW) (n) -NH2 (n = 1, 2, 3, 4, 5), and the antimicrobial activity and membrane interaction mechanism of the peptides were evaluated. The results showed that these peptides readily fold into beta-hairpin structures in aqueous and membrane-mimicking environments and exhibit broad-spectrum antimicrobial activities against both gram-positive and gram-negative bacteria. The antibacterial potency of the peptides initially increased and then decreased with increasing chain length. WK3, a 14-residue peptide, displayed excellent antimicrobial activity with minimal hemolytic activity and cytotoxicity, suggesting that it possesses great cell selectivity. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), fluorescence spectroscopy, and flow cytometry indicated that representative peptides WK3 and WK4 exert their activities by permeabilizing the microbial membrane and damaging cell membrane integrity. This study reveals the application potential of the designed peptides as promising antimicrobial agents for the control of infectious diseases, and it also provides new insights into the design and optimization of highly stable beta-hairpin AMPs with great antimicrobial activities and cell selectivities.
- 出版日期2015-11
- 单位东北农业大学
