Antimicrobial characterization of human β-defensin 3 derivatives
Antimicrobial characterization of human β-defensin 3 derivatives
复制标题
DOI：
10.1128/aac.47.9.2804-2809.2003
复制
发表时间：
2003-09-01
影响因子：
4.9
通讯作者：
Lubkowski, J
中科院分区：
文献类型：
--
作者：
Hoover, DM;Wu, ZB;Lubkowski, J
人β -防御素3 （hBD3）是一种高度碱性的45氨基酸蛋白，既可作为抗菌剂又可作为化学引诱分子。虽然其抗菌活性的性质主要是静电的，但分子结构对这种活性的重要性了解甚少。合成了hBD3的两种异构体：第一种具有天然二硫键，第二种具有规范键。在第三个合成肽中，所有半胱氨酸残基都被α -氨基丁酸取代，形成一个完全线性的肽。我们还合成了一系列与hBD3区域对应的6个小的线性肽，它们的净电荷在+4到+8之间（pH值为7），长度在9到20个氨基酸之间。线性全长肽对大肠杆菌和金黄色葡萄球菌的抑菌活性最高，对白色念珠菌的抑菌活性相同。该线状肽对粪肠球菌和铜绿假单胞菌也有较高的抑制活性。C端对应的肽对大肠杆菌具有较高的活性，且活性最强的肽是碱性最强的。然而，只有hBD3的N端对应的肽段显示出对金黄色葡萄球菌和白色念珠菌的活性。此外，天然hBD3的n端缺失突变体对金黄色葡萄球菌的活性降低。因此，hBD3衍生物的抗菌性能是由电荷和结构决定的。
Human beta-defensin 3 (hBD3) is a highly basic 45-amino-acid protein that acts both as an antimicrobial agent and as a chemoattractant molecule. Although the nature of its antimicrobial activity is largely electrostatic, the importance of the molecular structure on this activity is poorly understood. Two isoforms of hBD3 were synthesized: the first with native disulfide linkages and the second with normative linkages. In a third synthetic peptide, all cysteine residues were replaced with alpha-aminobutyric acid, creating a completely linear peptide. A series of six small, linear peptides corresponding to regions of hBD3 with net charges ranging from +4 to +8 (at pH 7) and lengths ranging from 9 to 20 amino acids were also synthesized. The linear full-length peptide showed the highest microbicidal activity against Escherichia coli and Staphylococcus aureus, while all three full-length forms showed equal activity against Candida albicans. The linear peptide also showed high activity against Enterococcus faecium and Pseudomonas aeruginosa.. Peptides corresponding to the C terminus showed higher activities when tested against E. coli, with the most active peptides being the most basic. However, only the peptide corresponding to the N terminus of hBD3 showed any activity against S. aureus and C. albicans. Further, N-terminal deletion mutants of native hBD3 showed diminished activities against S. aureus. Thus, the antimicrobial properties of hBD3 derivatives are determined by both charge and structure.