抗体疏水化片段通过血脑屏障的转运。

Transport of hydrophobized fragments of antibodies through the blood-brain barrier.

作者信息

Chekhonin V P, Ryabukhin I A, Zhirkov Y A, Kashparov I A, Dmitriyeva T B

机构信息

Laboratory of Immunochemistry, V. P. Serbsky National Research Center for Social and Forensic Psychiatry, Moscow, Russian Federation.

出版信息

Neuroreport. 1995 Dec 29;7(1):129-32.

PMID:8742434

Abstract

Hydrophobized and non-hydrophobized Fab fragments of human antibodies against gliofibrillar acid protein (GFAP) and brain specific alpha 2-glycoprotein (alpha 2GP) were used to study their penetration through the blood-brain barrier (BBB). These Fab fragments were modified by stearoyl chloride in reversed micelles of aerosol OT in octane (one or two fatty acid residues attached to protein molecule). Modified and non-modified 125I-labelled Fab fragments were intracardially administered to rats. The amount of label accumulated in brain was 55% higher than the total amount in all other organs. In contrast, non-hydrophobized Fab fragments did not penetrate through the BBB. We assume that the artificial hydrophobization of Fab fragments can increase their capability to penetrate through the cell membranes and, in particular, the BBB.

摘要

使用针对胶质纤维酸性蛋白（GFAP）和脑特异性α2 - 糖蛋白（α2GP）的人源抗体的疏水化和未疏水化Fab片段，来研究它们穿过血脑屏障（BBB）的情况。这些Fab片段在辛烷中的气溶胶OT反胶束中用硬脂酰氯进行修饰（一个或两个脂肪酸残基连接到蛋白质分子上）。将修饰和未修饰的125I标记的Fab片段经心内注射给大鼠。脑中积累的标记量比所有其他器官中的总量高55%。相比之下，未疏水化的Fab片段不能穿过血脑屏障。我们推测，Fab片段的人工疏水化可以提高它们穿透细胞膜，特别是血脑屏障的能力。