Cancer-Associated Gangliosides as a Therapeutic Target for Host Defense Peptide Mimics.
Cancer-Associated Gangliosides as a Therapeutic Target for Host Defense Peptide Mimics.
复制标题
DOI：
10.1021/acs.langmuir.3c01008
复制
发表时间：
2023-08
期刊：
影响因子：
--
通讯作者：
M. Martynowycz;Konstantin Andreev;A. Mor;D. Gidalevitz
中科院分区：
文献类型：
--
作者：
M. Martynowycz;Konstantin Andreev;A. Mor;D. Gidalevitz
细胞表面糖脂表达的异常水平是不同类型癌症的特征。模拟抗菌肽的酰化赖氨酸(OAK)低聚物具有上调的GD3和GM3神经节苷脂在体外对人和小鼠黑色素瘤细胞株的活性。在这里，我们证明了橡树有能力插层到唾液酸寡糖的DPPC/GD3和DPPC/GM3脂单分子层。没有插入到含有磷脂酰丝氨酸的单层中，这表明橡树对糖化脂膜的作用机制不仅仅是由电荷效应驱动的。荧光显微镜数据显示了橡木的溶膜活性。了解抗菌脂肽对GD3和GM3神经节苷脂选择性的分子基础将有助于开发治疗黑色素瘤和其他恶性肿瘤的新疗法。
Aberrant levels of glycolipids expressed on cellular surfaces are characteristic of different types of cancers. The oligomer of acylated lysine (OAK) mimicking antimicrobial peptides displays in vitro activity against human and murine melanoma cell lines with upregulated GD3 and GM3 gangliosides. Herein, we demonstrate the capability of OAK to intercalate into the sialo-oligosaccharides of DPPC/GD3 and DPPC/GM3 lipid monolayers using X-ray scattering. The lack of insertion into monolayers containing phosphatidylserine suggests that the mechanism of action by OAKs against glycosylated lipid membranes is not merely driven by charge effects. The fluorescence microscopy data demonstrates the membrane-lytic activity of OAK. Understanding the molecular basis for selectivity toward GD3 and GM3 gangliosides by antimicrobial lipopeptides will contribute to the development of novel therapies to cure melanoma and other malignancies.