小分子与磷脂双层的相互作用。一些与配体蛋白和氨基偶氮染料结合蛋白A结合的不带电荷分子（2-乙酰氨基芴、4-二甲基氨基偶氮苯、雌酮和睾酮）与鸡蛋卵磷脂的结合。

Interactions of small molecules with phospholipid bilayers. Binding to egg phosphatidylcholine of some uncharged molecules (2-acetylaminofluorene, 4-dimethylaminoazobenzene, oestrone and testosterone) that bind to ligandin and aminoazo-dye-binding protein A.

作者信息

Tipping E, Ketterer B, Christodoulides L

出版信息

Biochem J. 1979 May 15;180(2):319-26. doi: 10.1042/bj1800319.

DOI:10.1042/bj1800319

PMID:114168

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1161056/

Abstract

To assess the possible involvement of ligandin and aminoazo-dye-binding protein A in intracellular transport it is necessary to know how their ligands, most of which are molecules with hydrophobic moieties, interact with cellular membranes. To obtain such information we have examined the interactions of 2-acetylaminofluorene, 4-dimethylaminoazobenzene, oestrone and testosterone with aqueous dispersions of egg phosphatidylcholine and egg phosphatidylcholine/cholesterol (1:1, molar ratio) by equilibrium dialysis and spectrophotometry. 2. At 25 degrees C and pH7.4, the partition coefficients for binding to phosphatidylcholine [expressed as (mol of ligand bound/mol of phosphatidylcholine)/unbound ligand concentration] were: for 2-acetylaminofluorene, 5.0x10(3) litre.mol(-1); for 4-dimethylaminoazobenzene, 2.1x10(4) litre.mol(-1); for oestrone, 3.1x10(3) litre.mol(-1); and for testosterone, 4.2x10(2) litre.mol(-1). In the ranges studied these values were independent of concentration. The results for the two steroids confirm those of Heap, Symons & Watkins [(1970) Biochim. Biophys. Acta218, 482-495]. 3. The introduction of cholesterol into the lipid bilayers caused large decreases in the partition coefficients of oestrone and testosterone, but had relatively little effect on the binding of 2-acetylaminofluorene and 4-dimethylaminoazobenzene. 4. By assuming that the interactions with egg phosphatidylcholine bilayers resemble those with the phospholipid components of mammalian intracellular membranes the phosphatidylcholine partition coefficients, together with data for binding to the intracellular proteins ligandin and aminoazo-dye-binding protein A, enable the subcellular distributions of the four compounds to be estimated. For the rat hepatocyte up to 98, 99, 89 and 58% of the total 2-acetylaminofluorene, 4-dimethylaminoazobenzene, oestrone and testosterone respectively may be membrane-bound.

摘要

为评估配体蛋白和氨基偶氮染料结合蛋白A在细胞内转运中的可能作用，有必要了解它们的配体（其中大多数是带有疏水部分的分子）如何与细胞膜相互作用。为获取此类信息，我们通过平衡透析和分光光度法研究了2-乙酰氨基芴、4-二甲基氨基偶氮苯、雌酮和睾酮与鸡蛋磷脂酰胆碱及鸡蛋磷脂酰胆碱/胆固醇（摩尔比1:1）水分散体的相互作用。2. 在25℃和pH7.4条件下，与磷脂酰胆碱结合的分配系数[表示为（结合的配体摩尔数/磷脂酰胆碱摩尔数）/未结合配体浓度]分别为：2-乙酰氨基芴为5.0×10³升·摩尔⁻¹；4-二甲基氨基偶氮苯为2.1×10⁴升·摩尔⁻¹；雌酮为3.1×10³升·摩尔⁻¹；睾酮为4.2×10²升·摩尔⁻¹。在所研究的浓度范围内，这些值与浓度无关。两种类固醇的结果证实了希普、西蒙斯和沃特金斯[（1970年）《生物化学与生物物理学学报》218，482 - 495]的结果。3. 向脂质双层中引入胆固醇导致雌酮和睾酮的分配系数大幅降低，但对2-乙酰氨基芴和4-二甲基氨基偶氮苯的结合影响相对较小。4. 通过假设与鸡蛋磷脂酰胆碱双层的相互作用类似于与哺乳动物细胞内膜磷脂成分的相互作用，磷脂酰胆碱分配系数以及与细胞内蛋白配体蛋白和氨基偶氮染料结合蛋白A结合的数据，能够估算这四种化合物的亚细胞分布。对于大鼠肝细胞，2-乙酰氨基芴、4-二甲基氨基偶氮苯、雌酮和睾酮总量中分别可能有高达98%、99%、89%和58%与膜结合。