Epand R M, Epand R F, Richardson C D, Yeagle P L
Department of Biochemistry, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Biochim Biophys Acta. 1993 Oct 10;1152(1):128-34. doi: 10.1016/0005-2736(93)90239-v.
The peptide ZfFG is known to inhibit non-bilayer phase formation as well as vesicle-vesicle and viral fusion. In order to ascertain some of the properties or structural features of this peptide which were important for the inhibition of membrane fusion, the blocking group was transferred from the amino to the carboxyl end to make fFGOBz. The fFGOBz lowered the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine and it promoted the formation of isotropic phases in monomethyldioleoylphosphatidylethanolamine. The promotion of non-bilayer phases by fFGOBz appeared to be enhanced by a charged terminal amino group as higher pH or formylation of the amino group both decreased the effectiveness of this peptide to induce formation of the hexagonal phase. With the monomethyldioleoylphosphatidylethanolamine, the fFGOBz also promoted vesicle leakage and fusion as measured by lipid intermixing. The fFGOBz did not inhibit the formation of lipid structures of high curvature, resulting from sonication of phosphatidylcholine, as did ZfFG. Thus, the effects of fFGOBz on membranes are in sharp contrast to those of ZfFG and more closely resemble the behaviour of larger fusion peptides corresponding to the amino-terminal segment of viral fusion proteins. Our results demonstrate that having the carbobenzoxy group on the amino-terminus of fFG is important for giving the peptide derivative the property of inhibiting membrane fusion.
已知肽ZfFG可抑制非双层相形成以及囊泡-囊泡融合和病毒融合。为了确定该肽对膜融合抑制作用的一些重要特性或结构特征，将保护基团从氨基转移至羧基末端，制成fFGOBz。fFGOBz降低了二油酰磷脂酰乙醇胺的双层向六方相的转变温度，并促进了单甲基二油酰磷脂酰乙醇胺中各向同性相的形成。fFGOBz对非双层相的促进作用似乎因带电荷的末端氨基而增强，因为较高的pH值或氨基的甲酰化都会降低该肽诱导六方相形成的有效性。对于单甲基二油酰磷脂酰乙醇胺，通过脂质混合测定，fFGOBz还促进了囊泡泄漏和融合。与ZfFG不同，fFGOBz不会抑制由磷脂酰胆碱超声处理产生的高曲率脂质结构的形成。因此，fFGOBz对膜的作用与ZfFG形成鲜明对比，更类似于对应于病毒融合蛋白氨基末端片段的较大融合肽的行为。我们的结果表明，fFG的氨基末端带有苄氧羰基对于赋予肽衍生物抑制膜融合的特性很重要。
