Naturally occurring membranolytic antimicrobial peptides (AMPs) are rarely cell-type selective and highly potent at the same time. Template-based peptide design can be used to generate AMPs with improved properties de novo. Following this approach, 18 linear peptides were obtained by computationally morphing the natural AMP Aurein 2.2d2 GLFDIVKKVVGALG into the synthetic model AMP KLLKLLKKLLKLLK. Eleven of the 18 chimeric designs inhibited the growth of Staphylococcus aureus, and six peptides were tested and found to be active against one resistant pathogenic strain or more. One of the peptides was broadly active against bacterial and fungal pathogens without exhibiting toxicity to certain human cell lines. Solution nuclear magnetic resonance and molecular dynamics simulation suggested an oblique-oriented membrane insertion mechanism of this helical de novo peptide. Temperature-resolved circular dichroism spectroscopy pointed to conformational flexibility as an essential feature of cell-type selective AMPs.

中文翻译：

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两亲性螺旋的变形以探索膜分解抗菌肽的活性和选择性。

天然存在的膜分解抗微生物肽（AMPs）很少具有细胞类型的选择性，并且同时具有很高的效力。基于模板的肽设计可用于从头产生具有改进性质的AMP 。按照这种方法，通过将天然AMP Aurein 2.2d2 GLFDIVKKVVGALG计算变形为合成模型AMP KLLKLLKKLLKLLK，可以获得18个线性肽。18种嵌合设计中有11种抑制金黄色葡萄球菌的生长测试了6种肽，发现它们对一种或多种抗病原体具有活性。一种肽对细菌和真菌病原体具有广泛的活性，而对某些人细胞系没有毒性。溶液核磁共振和分子动力学模拟表明这种螺旋从头肽的倾斜定向膜插入机制。温度分辨圆二色性光谱指出构象柔性是细胞型选择性AMP的基本特征。