两亲性多肽聚（赖氨酸-α-氨基异丁酸-亮氨酸-α-氨基异丁酸）与脂质双层膜的pH依赖性相互作用

pH-dependent interaction of amphiphilic polypeptide poly(Lys-Aib-Leu-Aib) with lipid bilayer membrane.

作者信息

Kono K, Kimura S, Imanishi Y

机构信息

Department of Polymer Chemistry, Kyoto University, Japan.

出版信息

Biochemistry. 1990 Apr 17;29(15):3631-7. doi: 10.1021/bi00467a007.

DOI:10.1021/bi00467a007

PMID:2340263

Abstract

A sequential polypeptide, poly(Lys-Aib-Leu-Aib) (Aib represents 2-aminoisobutyric acid), was synthesized, and the interaction with lipid membrane was studied. Poly(Lys-Aib-Leu-Aib) was designed to take an amphiphilic structure upon the formation of alpha-helix. Circular dichroism of poly(Lys-Aib-Leu-Aib) in an aqueous solution showed a negative Cotton effect due to alpha-helix. The content of alpha-helix increased when the pH was raised above 7.5 or in the presence of small unilamellar vesicles composed of egg yolk lecithin. On the other hand, alpha-helical conformation was broken by increasing the ionic strength of solution. Carboxyfluorescein leakage from dipalmitoylphosphatidylcholine (DPPC) vesicles induced by binding of poly(Lys-Aib-Leu-Aib) to the lipid membrane was facilitated in an alkaline solution and/or in a solution of low ionic strength. These phenomena can be related to the alpha-helix content of the polypeptide. It was shown that poly(Lys-Aib-Leu-Aib) induced fusion of DPPC vesicles in an alkaline solution below the phase-transition temperature of the membrane. It was further shown that the aggregation and fusion of the neutral lipid membrane was regulated by changing the pH of solution.

摘要

合成了一种序列多肽聚（赖氨酸 - α-氨基异丁酸 - 亮氨酸 - α-氨基异丁酸）（α-氨基异丁酸代表2-氨基异丁酸），并研究了其与脂质膜的相互作用。聚（赖氨酸 - α-氨基异丁酸 - 亮氨酸 - α-氨基异丁酸）被设计成在形成α-螺旋时具有两亲结构。聚（赖氨酸 - α-氨基异丁酸 - 亮氨酸 - α-氨基异丁酸）在水溶液中的圆二色性显示由于α-螺旋产生负的科顿效应。当pH值升高到7.5以上或存在由蛋黄卵磷脂组成的小单层囊泡时，α-螺旋的含量增加。另一方面，溶液离子强度增加会破坏α-螺旋构象。聚（赖氨酸 - α-氨基异丁酸 - 亮氨酸 - α-氨基异丁酸）与脂质膜结合诱导二棕榈酰磷脂酰胆碱（DPPC）囊泡泄漏羧基荧光素在碱性溶液和/或低离子强度溶液中更容易发生。这些现象可能与多肽的α-螺旋含量有关。结果表明，聚（赖氨酸 - α-氨基异丁酸 - 亮氨酸 - α-氨基异丁酸）在低于膜相变温度的碱性溶液中诱导DPPC囊泡融合。进一步表明，通过改变溶液的pH值可以调节中性脂质膜的聚集和融合。