Pini Alessandro, Giuliani Andrea, Falciani Chiara, Fabbrini Monica, Pileri Silvia, Lelli Barbara, Bracci Luisa
Dipartimento di Biologia molecolare, Università degli Studi di Siena, Via Fiorentina 1, 53100, Siena, Italy.
J Pept Sci. 2007 Jun;13(6):393-9. doi: 10.1002/psc.858.
We analyzed functional activity of the antimicrobial peptide M6 in vitro and in vivo. The peptide was identified by our group by phage library selection, rational modification and synthesis in a tetrabranched form (Pini et al., Antimicrob. Agents Chemother. 2005; 49: 2665-72). We found that it binds lipopolysaccharide, causes perforation of cell membranes without destroying external cell morphology and strongly binds DNA. The latter feature suggests that it could inhibit metabolic pathways, blocking DNA replication and/or transcription. We also observed that M6 does not stimulate humoral immune response when repeatedly administered to animals. We also analyzed M6 toxicity when administered to animals by intraperitoneal or by intravenous injection, determining a preliminary LD50 (125 and 37.5 mg/kg, respectively), which suggested that M6 could be used in vivo. These features make the antimicrobial branched peptide M6 a promising candidate for the development of a new antibacterial drug.
我们在体外和体内分析了抗菌肽M6的功能活性。该肽由我们团队通过噬菌体文库筛选、合理修饰并以四分支形式合成鉴定得到（皮尼等人，《抗菌剂与化疗》，2005年；49: 2665 - 72）。我们发现它能结合脂多糖，导致细胞膜穿孔而不破坏细胞外部形态，并且能强烈结合DNA。后一特性表明它可能抑制代谢途径，阻断DNA复制和/或转录。我们还观察到，当对动物反复给药时，M6不会刺激体液免疫反应。我们还通过腹腔注射或静脉注射给动物使用M6后分析其毒性，确定了初步的半数致死量（分别为125和37.5毫克/千克），这表明M6可在体内使用。这些特性使抗菌分支肽M6成为开发新型抗菌药物的有前景的候选物。
