Helical peptoid mimics of magainin-2 amide
Helical peptoid mimics of magainin-2 amide
复制标题
DOI：
10.1021/ja037320d
复制
发表时间：
2003-10-08
影响因子：
15
通讯作者：
Barron, AE
中科院分区：
文献类型：
--
作者：
Patch, JA;Barron, AE
设计了一系列类肽寡聚物作为爪蟾抗菌肽-2酰胺抗菌肽的螺旋、阳离子和表面两亲性模拟物。我们使用圆二色光谱法来确定这些类肽在水性缓冲液中以及在细菌膜模拟脂囊泡（由摩尔比为7：3的POPE：POPG组成）存在下的构象。我们发现，某些类肽，显示特征性的螺旋CD缓冲液和脂质囊泡，表现出选择性（非溶血性）和有效的抗菌活性对革兰氏阳性和革兰氏阴性细菌。相比之下，表现出弱CD的类肽，让人想起肽无规卷曲，是无效的抗生素。以类似于天然爪蟾抗菌肽的方式，我们发现类肽亲脂性和溶血倾向之间存在相关性。我们观察到，抗菌活性可能需要最小长度的1012个类肽残基。我们还看到证据表明，螺旋长度在24和34 μ m之间可能提供最佳的抗菌功效。这些结果提供了水溶性、结构化、生物活性类肽的第一个实例。
A series of peptoid oligomers were designed as helical, cationic, and facially amphipathic mimics of the magainin-2 amide antibacterial peptide. We used circular dichroism spectroscopy to determine the conformation of these peptoids in aqueous buffer and in the presence of bacterial membrane-mimetic lipid vesicles, composed of a 7:3 mol ratio of POPE:POPG. We found that certain peptoids, which displayed characteristically helical CD in buffer and lipid vesicles, exhibit selective (nonhemolytic) and potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In contrast, peptoids that exhibit weak CD, reminiscent of that of a peptide random coil, were ineffective antibiotics. In a manner similar to the natural magainin peptides, we find a correlation between peptoid lipophilicity and hemolytic propensity. We observe that a minimum length of ∼12 peptoid residues may be required for antibacterial activity. We also see evidence that a helix length between 24 and 34 Å may provide optimal antibacterial efficacy. These results provide the first example of a water-soluble, structured, bioactive peptoid.