Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, NC 28403, USA.
J Membr Biol. 2013 Mar;246(3):257-62. doi: 10.1007/s00232-013-9525-z. Epub 2013 Jan 18.
Understanding the mechanisms of antimicrobial, cytolytic and cell-penetrating peptides is important for the design of new peptides to be used as cargo-delivery systems or antimicrobials. But these peptides should not be hemolytic. Recently, we designed a series of such membrane-active peptides and tested several hypotheses about their mechanisms on model membranes. To that end, the Gibbs free energy of binding to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles was determined experimentally. Because the main lipid components of the outermost monolayer of erythrocyte membranes are zwitterionic, like POPC, we hypothesized that the Gibbs free energy of binding of these peptides to POPC would also be a good indicator of their hemolytic activity. Now, the hemolytic activity of those synthetic peptides was examined by measuring the lysis of sheep erythrocyte suspensions after peptide addition. Indeed, the Gibbs free energy of binding was in good correlation with the hemolytic activity, which was represented by the concentration of peptide in solution that produced 50 % hemolysis. Furthermore, with two exceptions, those peptides that caused graded dye release from POPC vesicles were also hemolytic, while most of those that caused all-or-none release were not.
了解抗菌、溶细胞和细胞穿透肽的作用机制对于设计用作货物输送系统或抗菌剂的新肽至关重要。但这些肽不应具有溶血活性。最近，我们设计了一系列这样的膜活性肽，并在模型膜上测试了关于其机制的几个假设。为此，我们通过实验确定了与 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱 (POPC) 囊泡结合的吉布斯自由能。由于红细胞膜最外层单层的主要脂质成分与 POPC 一样是两性离子，因此我们假设这些肽与 POPC 结合的吉布斯自由能也将是其溶血活性的良好指标。现在，通过测量肽加入后绵羊红细胞悬浮液的溶血来检查这些合成肽的溶血活性。实际上，结合的吉布斯自由能与溶血活性很好地相关，溶血活性由产生 50%溶血的溶液中肽的浓度表示。此外，除了两个例外，从 POPC 囊泡中引起分级染料释放的那些肽也是溶血的，而大多数引起全或无释放的肽则不是。
