Helical peptoid mimics of magainin-2 amide

被引:327
作者
Patch, JA [1 ]
Barron, AE [1 ]
机构
[1] Northwestern Univ, Dept Chem Engn, Evanston, IL 60208 USA
关键词
D O I
10.1021/ja037320d
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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. Copyright © 2003 American Chemical Society.
引用
收藏
页码:12092 / 12093
页数:2
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