Mimics of natural antimicrobial peptides are promising compounds to fight the rising threat of multi‐drug resistant bacteria. Here we report the design, synthesis and conformational analysis of a new class of antimicrobial peptide mimetics incorporating a diphenylacetylene scaffold. Within a small set of compounds, we observe a correlation between amphiphilicity, the efficiency of partitioning into negatively charged membranes and antibacterial activity. The most amphiphilic compound, which contains four isoleucine residues and four lysine residues, displays species‐selective antibacterial activity (most active against Bacillus subtills) and low haemolytic activity. Solution‐phase conformational analysis of this compound indicates that a defined structure is adopted in the presence of negatively charged phospholipid membranes and aqueous 2,2,2‐trifluoroethanol but not in water. A conformation model indicates that the cationic and hydrophobic functional groups are segregated. These results may inform the development of highly selective antimicrobial peptide mimetics for therapeutic applications.

中文翻译：

---

基于二苯乙炔支架的抗菌肽模拟物：合成、构象分析和活性。

天然抗菌肽的模拟物是对抗多重耐药菌日益严重的威胁的有希望的化合物。在这里，我们报告了一类新的包含二苯乙炔支架的抗菌肽模拟物的设计、合成和构象分析。在一小部分化合物中，我们观察到两亲性、带负电荷膜的分配效率和抗菌活性之间的相关性。最具两亲性的化合物，包含四个异亮氨酸残基和四个赖氨酸残基，显示出物种选择性抗菌活性（对枯草芽孢杆菌最活跃）) 和低溶血活性。该化合物的溶液相构象分析表明，在带负电荷的磷脂膜和 2,2,2-三氟乙醇水溶液存在下采用确定的结构，但在水中不采用。构象模型表明阳离子和疏水官能团是分离的。这些结果可能有助于开发用于治疗应用的高选择性抗菌肽模拟物。