...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Peptoid-Substituted Hybrid Antimicrobial Peptide Derived from Papiliocin and Magainin 2 with Enhanced Bacterial Selectivity and Anti-inflammatory Activity
【24h】

Peptoid-Substituted Hybrid Antimicrobial Peptide Derived from Papiliocin and Magainin 2 with Enhanced Bacterial Selectivity and Anti-inflammatory Activity

机译：衍生自Papiliocin和Magainin 2的类肽取代杂合抗菌肽，具有增强的细菌选择性和抗炎活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Antimicrobial peptides (AMPs) are important components of the host innate immune system. Papiliocin is a 37-residue AMP purified from larvae of the swallowtail butterfly Papilio xuthus. Magainin 2 is a 23-residue AMP purified from the skin of the African clawed frog Xenopus laevis. We designed an 18-residue hybrid peptide (PapMA) incorporating N-terminal residues 1-8 of papiliocin and N-terminal residues 4-12 of magainin 2, joined by a proline (Pro) hinge. PapMA showed high antimicrobial activity but was cytotoxic to mammalian cells. To decrease PapMA cytotoxicity, we designed a lysine (Lys) peptoid analogue, PapMA-k, which retained high antimicrobial activity but displayed cytotoxicity lower than that of PapMA. Fluorescent dye leakage experiments and confocal microscopy showed that PapMA targeted bacterial cell membranes whereas PapMA-k penetrated bacterial cell membranes. Nuclear magnetic resonance experiments revealed that PapMA contained an N-terminal alpha-helix from Lys(3) to Lys(7) and a C-terminal alpha-helix from Lys(10) to Lys(17), with a Pro(9) hinge between them. PapMA-k also had two alpha-helical structures in the same region connected with a flexible hinge residue at Nlys(9), which existed in a dynamic equilibrium of cis and trans conformers. Using lipopolysaccharide-stimulated RAW264.7 macrophages, the anti-inflammatory activity of PapMA and PapMA-k was confirmed by inhibition of nitric oxide and inflammatory cytokine production. In addition, treatment with PapMA and PapMA-k decreased the level of ultraviolet irradiation-induced expression of genes encoding matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in human keratinocyte HaCaT cells. Thus, PapMA and PapMA-k are potent peptide antibiotics with antimicrobial and anti-inflammatory activity, with PapMA-k displaying enhanced bacterial selectivity.
机译：抗菌肽（AMPs）是宿主先天免疫系统的重要组成部分。 Papiliocin是从燕尾蝴蝶Papilio xuthus的幼虫中纯化的37个残基的AMP。 Magainin 2是从非洲爪蛙Xenopus laevis皮肤中纯化的23个残基AMP。我们设计了一个18个残基的杂合肽（PapMA），该肽结合了木瓜素的N末端残基1-8和magainin 2的N末端残基4-12，通过脯氨酸（Pro）铰链连接。 PapMA显示高抗菌活性，但对哺乳动物细胞具有细胞毒性。为了降低PapMA的细胞毒性，我们设计了赖氨酸（Lys）拟肽类似物PapMA-k，该类似物保留了较高的抗菌活性，但显示出的细胞毒性低于PapMA。荧光染料泄漏实验和共聚焦显微镜显示，PapMA靶向细菌细胞膜，而PapMA-k穿透细菌细胞膜。核磁共振实验表明，PapMA包含一个从Lys（3）到Lys（7）的N端α-螺旋和一个从Lys（10）到Lys（17）的C端α-螺旋，以及一个Pro（9）它们之间的铰链。 PapMA-k在同一区域还具有两个α-螺旋结构，与Nlys（9）处的柔性铰链残基相连，该残基以顺式和反式构象异构体的动态平衡存在。使用脂多糖刺激的RAW264.7巨噬细胞，通过抑制一氧化氮和炎性细胞因子的产生，证实了PapMA和PapMA-k的抗炎活性。此外，用PapMA和PapMA-k处理可降低紫外线照射诱导的编码基质金属蛋白酶-1（MMP-1），白介素-6（IL-6）和肿瘤坏死因子-α（TNF- α）在人类角质形成细胞的HaCaT细胞中。因此，PapMA和PapMA-k是具有抗菌和抗炎活性的有效肽类抗生素，PapMA-k显示出增强的细菌选择性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号