目前的癌症治疗破坏健康细胞和组织，引起短期和长期的副作用。需要新的治疗方法，表现出更好的肿瘤细胞选择性，并回避常见的多药耐药机制。膜溶解型抗癌肽（mACPs）对抗癌症和多药耐药具有潜力。mACPs的两性性、疏水性和净电荷参与其与细胞膜的相应相互作用及对癌细胞的整体抑制。为了支持细胞系选择性mACPs的设计，我们研究了氨基酸组成、物理化学性质、序列模式和序列同源性与其对多个健康和癌细胞系的效力和选择性之间的关系。序列长度和净电荷已知会影响mACPs在癌症和健康细胞系之间的选择性。我们的研究发现，增加净电荷或灵活性（即小的和脂肪族残基）会影响它们在具有相似脂质组成的癌细胞系之间的选择性。© 2023 Wiley-VCH GmbH。

Current cancer treatments damage healthy cells and tissues, causing short-term and long-term side effects. New treatments are desired that show greater selectivity toward cancer cells and evade the common mechanisms of multidrug resistance. Membranolytic anticancer peptides (mACPs) hold promise against cancer and multidrug resistance. Amphipathicity, hydrophobicity, and net charge of mACPs participate in their respective interactions with cell membranes and their overall inhibition of cancer cells. To support the design of cell-line selective mACPs, we investigated the relationships that amino acid composition, physicochemical properties, sequence motifs and sequence homology could have with their potency and selectivity towards several healthy and cancer cell lines. Sequence length and net charge are known to affect the selectivity of mACPs between cancer and healthy cell lines. Our study reveals that increasing the net charge or flexibility (i.e., small and aliphatic residues) influences their selectivity between cancer cell lines with comparable lipid compositions.© 2023 Wiley-VCH GmbH.