Duval Emilie, Zatylny Céline, Laurencin Mathieu, Baudy-Floc'h Michèle, Henry Joël
UMR 100 IFREMER Physiologie et Ecophysiologie des Mollusques Marins, Université de Caen, Caen cedex, France.
Peptides. 2009 Sep;30(9):1608-12. doi: 10.1016/j.peptides.2009.06.022. Epub 2009 Jun 30.
With 14 residues organized as two domains linked by a single proline, the de novo peptide called K4 was designed, using Antimicrobial Peptide Database, to exert antibacterial activity. The N-terminal domain is composed of four lysines enhancing membrane interactions, and the C-terminal domain is putatively folded into a hydrophobic alpha-helix. Following the synthesis, the purification and the structural checking, antibacterial assays revealed a strong activity against gram-positive and gram-negative bacteria including human pathogenic bacteria such as Staphylococcus aureus and some marine bacteria of the genus Vibrio. Scanning electron microscopy of Escherichia coli confirmed that K4 lyses bacterial cells. The cytotoxicity was tested against rabbit erythrocytes and chinese hamster ovary cells (CHO-K1). These tests revealed that K4 is non-toxic to mammalian cells for bacteriolytic concentrations. The peptide K4 could be a valuable candidate for future therapeutic applications.
通过将14个残基组织成由单个脯氨酸连接的两个结构域,利用抗菌肽数据库设计了一种名为K4的从头合成肽,以发挥抗菌活性。N端结构域由四个赖氨酸组成,增强了与膜的相互作用,C端结构域推测折叠成一个疏水的α螺旋。合成、纯化和结构检查后,抗菌试验显示对革兰氏阳性菌和革兰氏阴性菌具有很强的活性,包括人类病原菌如金黄色葡萄球菌和一些弧菌属的海洋细菌。大肠杆菌的扫描电子显微镜证实K4可裂解细菌细胞。针对兔红细胞和中国仓鼠卵巢细胞(CHO-K1)测试了细胞毒性。这些测试表明,对于溶菌浓度,K4对哺乳动物细胞无毒。肽K4可能是未来治疗应用的一个有价值的候选物。