Improved Antibacterial Activity of the Marine Peptide N6 against Intracellular Salmonella Typhimurium by Conjugating with the Cell-Penetrating Peptide Tat11 via a Cleavable Linker
Improved Antibacterial Activity of the Marine Peptide N6 against Intracellular Salmonella Typhimurium by Conjugating with the Cell-Penetrating Peptide Tat11 via a Cleavable Linker
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通过可裂解接头与细胞穿透肽 Tat11 结合，提高海洋肽 N6 对细胞内鼠伤寒沙门氏菌的抗菌活性
DOI：
10.1021/acs.jmedchem.8b01079
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发表时间：
2018-09-13
影响因子：
7.3
通讯作者：
Wang, Jianhua
中科院分区：
文献类型：
--
作者：
Li, Zhanzhan;Teng, Da;Wang, Jianhua
抗菌剂的渗透能力差限制了其在治疗细胞内细菌中的应用。在本研究中，通过组织蛋白酶可裂解的接头连接细胞穿透肽Tat（11）（1）和海洋肽N6（2）生成缀合物CNC（6），并首先设计和合成C端胺化的N6（7）和CNC（8）以消除细胞内鼠伤寒沙门氏菌。 6的细胞摄取率和7的稳定性均高于2，并且缀合物6、8和7几乎没有溶血和细胞毒性。 6、8、7对RAW264.7细胞中鼠伤寒沙门氏菌的抗菌活性分别增加67.2-76.2%、98.6-98.9%、96.3-97.6%。用1-2μmol/kg的6、8、7处理后，鼠伤寒沙门氏菌感染小鼠的存活率为66.7-100%，高于2的存活率（33.4-66.7%）。这一结果表明6、8和7可能是治疗细胞内病原体的新型抗菌剂的优秀候选者。
The poor penetration ability of antimicrobial agents limits their use in the treatment of intracellular bacteria. In this study, the conjugate CNC (6) was generated by connecting the cell-penetrating peptide Tat(11) (1) and marine peptide N6 (2) via a cathepsin-cleavable linker, and the C-terminal aminated N6 (7) and CNC (8) were first designed and synthesized to eliminate intracellular Salmonellae Typhimurium. The cellular uptake of 6 and stability of 7 were higher than those of 2, and conjugates 6, 8, and 7 had almost no hemolysis and cytotoxicity. The antibacterial activities of 6, 8, and 7 against S. Typhimurium in RAW264.7 cells were increased by 67.2-76.2%, 98.6-98.9%, and 96.3-97.6%, respectively. After treatment with 1-2 mu mol/kg of 6, 8, or 7, the survival of the S. Typhimurium-infected mice was 66.7-100%, higher than that of 2 (33.4-66.7%). This result suggested that 6, 8, and 7 may be excellent candidates for novel antimicrobial agents to treat intracellular pathogens.