Olivieri Cristina, Bugli Francesca, Menchinelli Giulia, Veglia Gianluigi, Buonocore Francesco, Scapigliati Giuseppe, Stocchi Valentina, Ceccacci Francesca, Papi Massimiliano, Sanguinetti Maurizio, Porcelli Fernando
Department for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia L.go dell'Universita' snc 01100 Viterbo Italy
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Minneapolis 55455 USA.
RSC Adv. 2018 Dec 12;8(72):41331-41346. doi: 10.1039/c8ra08065h. eCollection 2018 Dec 7.
Starting from the sequence of the amphipathic α-helix of chionodracine (Cnd, 22 amino acids), we designed a series of mutants to increase Cnd's antimicrobial activity and selectivity toward prokaryotic cells and drug-resistant bacterial pathogens. We characterized these new Cnd-derived peptides using fluorescence, CD spectroscopy, and transmission electron microscopy, studying their interactions with synthetic lipid vesicles and assaying their biological function against , , , , , and sp. Upon interaction with model membranes, these new peptides with higher net charges and hydrophobic moments adopt a helical conformation similar to Cnd. Notably, they display a low cytotoxic activity against human primary cells, a low hemolytic activity, but a significantly high bactericidal activity against drug-resistant bacterial pathogens. The low values of micromolar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) make these Cnd-derived peptides potential templates to develop antimicrobial agents against drug-resistant human pathogens.
从雪蟹肽（Cnd，22个氨基酸）的两亲性α-螺旋序列出发，我们设计了一系列突变体，以提高Cnd对原核细胞和耐药细菌病原体的抗菌活性及选择性。我们利用荧光、圆二色光谱和透射电子显微镜对这些新的Cnd衍生肽进行了表征，研究它们与合成脂质囊泡的相互作用，并测定它们对[具体细菌名称未给出]和[具体细菌名称未给出]的生物学功能。与模型膜相互作用时，这些具有更高净电荷和疏水矩的新肽会采用类似于Cnd的螺旋构象。值得注意的是，它们对人原代细胞显示出低细胞毒性活性、低溶血活性，但对耐药细菌病原体具有显著高的杀菌活性。微摩尔级的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）的低值使得这些Cnd衍生肽成为开发针对耐药人类病原体的抗菌剂的潜在模板。
