Kang J H, Shin S Y, Jang S Y, Lee M K, Hahm K S
Peptide Engineering Research Unit, Korea, Research Institute of Bioscience and Biotechnology, Yusong, Taejon.
J Pept Res. 1998 Jul;52(1):45-50. doi: 10.1111/j.1399-3011.1998.tb00651.x.
The membrane-disrupting properties of cecropin A (1-8)-magainin 2 (1-12) hybrid peptide, which has higher antitumor with less hemolytic activities than cecropin A (1-8)-melittin (1-12), and its analogues were assessed by measuring the induced release of vesicle-entrapped fluorescence probes. A model membrane was made of zwitterionic phospholipid (phosphatidylcholine) or the mixture of negatively and zwitterionic phospholipids (phosphatidylcholine and phosphatidylserine). The extent of leakage of the aqueous content of the phospholipid vesicles was found to have remarkable discrepancies according to the amphipathic nature of each analogue peptide. The entrapped high molecular weight solute (fluorescein-labeled immunoglobulin G, 55 kDa) also was released by the analogue which had the largest hydrophobic region and the highest amphipathic score among peptides tested. As the result of the determination of the relationships between the membrane-disrupting properties and the hydrophobicity values of peptides, it was found that the membrane-disrupting activity increased according to increasing the hydrophobicity of the peptide. The tryptophan fluorescence emission spectra and CD spectra showed that on interaction with the phospholipid vesicle, the peptide acquired the ordered structure and alpha-helical conformation by moving a tryptophan residue into the nonpolar environment of the phospholipid vesicle. These results suggest that the breakdown of the lipid bilayer was mediated by the alpha-helical amphipathic structure of the peptide interacting with the lipid bilayers as well as the by the hydrophobicity of the peptide.
天蚕素A（1-8）-蛙皮素2（1-12）杂合肽及其类似物具有比天蚕素A（1-8）-蜂毒肽（1-12）更高的抗肿瘤活性且溶血活性更低的特性，通过测量囊泡包裹的荧光探针的诱导释放来评估其膜破坏特性。模型膜由两性离子磷脂（磷脂酰胆碱）或带负电荷和两性离子磷脂的混合物（磷脂酰胆碱和磷脂酰丝氨酸）制成。根据每种类似物肽的两亲性质，发现磷脂囊泡水性内容物的泄漏程度存在显著差异。在测试的肽中，具有最大疏水区域和最高两亲性得分的类似物也能释放包裹的高分子量溶质（荧光素标记的免疫球蛋白G，55 kDa）。通过测定肽的膜破坏特性与疏水性值之间的关系，发现膜破坏活性随着肽疏水性的增加而增加。色氨酸荧光发射光谱和圆二色光谱表明，与磷脂囊泡相互作用时，肽通过将一个色氨酸残基移动到磷脂囊泡的非极性环境中而获得有序结构和α-螺旋构象。这些结果表明，脂质双层的破坏是由肽与脂质双层相互作用的α-螺旋两亲结构以及肽的疏水性介导的。
