Chen Long, Zhang Qiang, Yuan Xiushuang, Cao Yimeng, Yuan Yanyan, Yin Huiwei, Ding Xiufang, Zhu Zhentai, Luo Shi-Zhong
Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.
Int J Biochem Cell Biol. 2017 Feb;83:71-75. doi: 10.1016/j.biocel.2016.12.011. Epub 2016 Dec 21.
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.
溶细胞肽和细胞穿透肽（CPPs）都是具有相似物理化学性质的膜活性肽。尽管它们各自的功能已得到深入研究，但这两类肽内在性质的差异却很少被讨论。在本研究中，我们通过改变螺旋轮投影上以及序列上的电荷分布，设计了一系列最近发现的CPP ZXR-1（FKIGGFIKKLWRSKLA）的类似物。这些肽在细胞膜上表现出不同的功能，包括膜溶解（肽Z1）、细胞穿透（肽ZXR-1、Z2和Z3）以及无活性（肽Z4）的肽。这三组肽与模型脂质单层表现出不同的相互作用，并发现肽的插入可能是区分溶解和细胞穿透功能的一个重要动态步骤。基于对电荷分布模式的分析，提出螺旋轮上以及序列上的电荷分布都能够影响膜活性肽的功能。这一发现进一步加深了对电荷分布对膜活性肽功能影响的理解，并将有助于功能性肽的设计。
