Antimicrobial peptides often show broad-spectrum activity due to a mechanism based on bacterial membrane disruption, which also reduces development of permanent resistance, a desirable characteristic in view of the escalating multidrug resistance problem. Host cell toxicity however requires design of artificial variants of natural AMPs to increase selectivity and reduce side effects. Kiadins were designed using rules obtained from natural peptides active against E. coli and a validated computational algorithm based on a training set of such peptides, followed by rational conformational alterations. In vitro activity, tested against ESKAPE strains (ATCC and clinical isolates), revealed a varied activity spectrum and cytotoxicity that only in part correlated with conformational flexibility. Peptides with a higher proportion of Gly were generally less potent and caused less bacterial membrane alteration, as observed by flow cytometry and AFM, which correlate to structural characteristics as observed by circular dichroism spectroscopy and predicted by molecular dynamics calculations.

中文翻译：

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甘氨酸-赖氨酸的α-螺旋抗菌肽的构象柔韧性影响抗菌活性

由于基于细菌膜破坏的机制，抗菌肽通常表现出广谱活性，这也减少了持久性耐药性的发展，这是考虑到多药耐药性问题不断升级的理想特征。然而，宿主细胞毒性需要设计天然AMP的人工变体，以提高选择性并减少副作用。使用从对大肠杆菌有活性的天然肽中获得的规则设计抗凝蛋白以及基于此类肽的训练集并经过合理构象改变的经过验证的计算算法。针对ESKAPE菌株（ATCC和临床分离株）进行的体外活性测试显示，其变化的活性谱和细胞毒性仅与构象柔韧性部分相关。通过流式细胞仪和原子力显微镜观察，具有较高Gly比例的肽通常效力较低，并引起较少的细菌膜改变，这与通过圆二色光谱观察并通过分子动力学计算预测的结构特征相关。