Division of Biophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, D-23845, Borstel, Germany.
J Pept Sci. 2013 Oct;19(10):619-28. doi: 10.1002/psc.2540. Epub 2013 Jul 25.
Equine sarcoid is a topically accessible model for the evaluation of anticancer peptides acting by physical membrane disruption avoiding the complexity of a systemic application. We aim at evaluating and improving natural peptides for host defence as lead structures, where we focus on the cationic and amphipathic peptide NK-2. Cytotoxicity tests, fluorescence microscopy and a chip-based biosensor, which enabled real-time monitoring of cell metabolism, were applied. Cancer cell killing was dynamic with an initial phase of increased cellular respiration, followed by membrane destruction. NK-2 was substantially improved and shortened. Novel peptides exhibited a fivefold improved activity against sarcoid cells, while haemolysis remained almost unaltered. Similar Zeta potential and similar amount of surface phosphatidylserine of sarcoid and normal skin cells are responsible for a lack of selectivity between these two cell types.
马的肉瘤是评估通过物理膜破坏作用的抗癌肽的一种具有吸引力的模型，可避免系统应用的复杂性。我们旨在评估和改进天然肽作为宿主防御的先导结构，其中我们专注于阳离子和两亲肽 NK-2。应用了细胞毒性试验、荧光显微镜和基于芯片的生物传感器，可实时监测细胞代谢。癌细胞杀伤具有动态性，最初阶段细胞呼吸增加，随后膜破坏。NK-2 得到了实质性的改进和缩短。新型肽对肉瘤细胞的活性提高了五倍，而溶血几乎不变。肉瘤和正常皮肤细胞的相似 Zeta 电位和相似数量的表面磷脂酰丝氨酸导致这两种细胞类型之间缺乏选择性。
