富含脯氨酸的抗菌肽研究进展

Recent research advances of Pro-rich antimicrobial peptides

富含脯氨酸的抗菌肽是一族分离自动物的线性多肽 ,它们都具有抗菌活性 ,在天然免疫中具有重要的作用。这类抗菌肽按来源又分为两类 :来自哺乳动物的富含脯氨酸的抗菌肽和来自昆虫和其他脊椎动物的富含脯氨酸的抗菌肽。它们都富含脯氨酸 ,对革兰阴性菌起作用 ,其杀菌机制不同于大多抗菌肽的膜溶解作用。它们进入细菌胞质后 ,结合DnaK蛋白 ,抑制DnaK的生物功能 ,最终导致了细菌的死亡。这一作用机制对于药物的开发很有意义。除了抗菌作用外 ,富含脯氨酸的抗菌肽还具有其他重要的药理作用。对这方面作用研究比较多的是PR 39,它在诱导粘连蛋白聚糖在间充质细胞的表达 ,抑制嗜中性粒细胞NADPH氧化酶 ,抑制 1κBα和HIF 1α的降解等方面具有重要作用。这些发现表明PR 39在伤口修复、炎症、缺血再灌注损伤以及诱导血管生成等方面具有很好的应用前景。

Pro-rich antimicrobial peptides are a group of linear peptides isolated from animals. These peptides have antibacterial activities and play an important role in innate immunity. Pro-rich antimicrobial peptides are devided into two classes:Pro-rich antimicrobial peptides from mammals and Pro-rich antimicrobial peptides from insects and other invertebrates.Members of Pro-rich antimicrobial peptides are all characterised by a high content of proline residues and predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism,at variance with the majority of the known antimicrobial peptides. Evidence is accumulating that the Pro-rich peptides enter the cells without membrane lysis and,once in the cytoplasm,bind to,and inhibit the activity of DnaK protein that is essential to bacterial growth,thereby causing responsive bacteria death. This mode of action makes these peptides suitable for drug development efforts. As one of the best characterized Pro-rich peptides,PR-39 plays an important role in a number of biological processes. It has been found that PR-39 can induce the syndecan expression in mesenchymal cells, inhibit the NADPH oxidase activity of neutrophils and block the degradation of 1κBα and HIF-1α. These findings show that PR-39 can provide novel means in the control of inflammation, wound repair, ischemia-reperfusion injury,and angiogenesis for therapeutic purposes.