Stoilova T B, Dutseva E A, Pashkovskaia A A, Sychev S V, Koval'chuk S I, Sobko A A, Egorova N S, Kotova E A, Antonenko Iu N, Surovoi A Iu, Ivanov V T
Bioorg Khim. 2007 Sep-Oct;33(5):511-9. doi: 10.1134/s1068162007050032.
The channel-forming activity of gramicidin A derivatives carrying positively charged amino acid sequences at their C-termini was studied on planar bilayer lipid membranes and liposomes. We showed previously that, at low concentrations, these peptides form classical cation-selective pores typical of gramicidin A, whereas, at high concentrations, they form large nonselective pores. The ability of the peptides to form nonselective pores, which was determined by the efflux of carboxyfluorescein, an organic dye, from liposomes, decreased substantially as the length of the gramicidin fragment in the series of cationic analogues was truncated. CD spectra showed that large pores are formed by peptides having both beta6.3 single-stranded and beta5.6 double-stranded helical conformations of the gramicidin fragment, with the C-terminal cationic sequence being extended. The dimerization of the peptides by the oxidation of the terminal cysteine promoted the formation of nonselective pores. It was shown that nonselective pores are not formed in membranes of erythrocytes, which may indicate a dependence of the channel-forming ability on the membrane type. The results may be of interest for the directed synthesis of peptides with antibacterial activity.
对在其C末端带有带正电荷氨基酸序列的短杆菌肽A衍生物的通道形成活性，在平面双层脂质膜和脂质体上进行了研究。我们之前表明，在低浓度下，这些肽形成典型的短杆菌肽A的经典阳离子选择性孔，而在高浓度下，它们形成大的非选择性孔。肽形成非选择性孔的能力，通过有机染料羧基荧光素从脂质体中的流出量来确定，随着阳离子类似物系列中短杆菌肽片段长度的截短而大幅下降。圆二色光谱表明，大孔由具有短杆菌肽片段的β6.3单链和β5.6双链螺旋构象的肽形成，C末端阳离子序列是伸展的。通过末端半胱氨酸的氧化使肽二聚化促进了非选择性孔的形成。结果表明，在红细胞膜中不形成非选择性孔，这可能表明通道形成能力对膜类型的依赖性。这些结果可能对具有抗菌活性的肽的定向合成具有意义。
