How charge distribution influences the function of membrane-active peptides: Lytic or cell-penetrating?

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• 作者：Long Chen¹ ; ^a ; Qiang Zhang¹ ; ^a ; Xiushuang Yuan¹ ; ^a ; Yimeng Cao^a ; Yanyan Yuan^a ; Huiwei Yin^a ; Xiufang Ding^a ; Zhentai Zhu^b ; Shi-Zhong Luo^a ; ^{luosz@mail.buct.edu.cn}
• 关键词：Lytic peptides ; Cell penetrating peptides ; Charge distribution ; Peptide-membrane interactions ; Peptide design
• 刊名：The International Journal of Biochemistry & Cell Biology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：83
• 期：Complete
• 页码：71-75
• 全文大小：1378 K
• 卷排序：83

文摘

Lytic and cell-penetrating peptides (CPPs) are both membrane-active peptides sharing similar physicochemical properties. Although their respective functions have been intensively investigated, the difference of intrinsic properties between these two types of peptides is rarely discussed. In this study, we designed a series of analogs of a recently discovered CPP ZXR-1 (FKIGGFIKKLWRSKLA) by varying the charge distributions both on the helical wheel projection and along the sequence. These peptides showed different functions on cell membranes, including membrane lytic (peptide Z1), cell-penetrating (peptide ZXR-1, Z2 and Z3), and inactive (peptide Z4) peptides. The three groups of peptides displayed different interactions with model lipid monolayer, and found that peptide insertion might be an important dynamic step to distinguish lytic and cell penetrating functions. Based on the analysis of charge distribution patterns, it was proposed that the charge distributions on the helical wheel and along the sequence are both able to influence the functions of the membrane-active peptides. This finding provides a further understanding about the effect of charge distribution on the functions of membrane-active peptides, and will be helpful for the design of functional peptides.