Development of a novel molecular adapter for the optimization of immunotoxins

被引：18

作者：

Keller, J ^{[1
]}

Heisler, I ^{[1
]}

Tauber, R ^{[1
]}

Fuchs, H ^{[1
]}

机构：

[1] Free Univ Berlin, Klinikum Benjamin Franklin, Inst Klin Chem & Pathobiochem, D-12200 Berlin, Germany

来源：

JOURNAL OF CONTROLLED RELEASE | 2001年 / 74卷 / 1-3期

关键词：

drug targeting; immunotoxin diphtheria toxin; trojan peptide;

D O I：

10.1016/S0168-3659(01)00329-7

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Immunotoxins consisting of catalytic domains of natural toxins and tumor-specific ligands were modified by introducing a molecular adapter that is able to transport the toxic domain more efficiently into cells. The adapter is a three-component structure: its core is a membrane transfer sequence (NITS) flanked by two different cleavable sequences. The directed and irreversible cellular uptake of the construct is driven by either enzymatic or chemical cleavage of the two flanking sequences. In our studies, the purified A-chain of diphtheria toxin (DT) was coupled to two different MTSs via disulfide bonds. A cytotoxicity assay revealed that the constructs containing the MTSs were more potent than DT A-chain alone and that the disulfide bond was cleaved. (C) 2001 Elsevier Science B.V. Ali rights reserved.

引用

页码：259 / 261

页数：3

共 5 条

[1]

DIGNAM JD, 1983, METHOD ENZYMOL, V101, P582

[2]

MOSKAUG JO, 1989, J BIOL CHEM, V264, P15709

[3] DETECTION OF TUMOR-SPECIFIC CYTOTOXIC DRUG ACTIVITY IN-VITRO USING THE FLUOROMETRIC MICROCULTURE CYTOTOXICITY ASSAY AND PRIMARY CULTURES OF TUMOR-CELLS FROM PATIENTS [J].