New chemical adaptor unit designed to release a drug from a tumor targeting device by enzymatic triggering

被引:23
作者
Gopin, A
Rader, C
Shabat, D [1 ]
机构
[1] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel
[2] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA
关键词
prodrug; self-immolative; enzyme; cancer;
D O I
10.1016/j.bmc.2004.01.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A new controlled drug delivery system for selective chemotherapy was developed. It is based on a chemical adaptor unit, that releases a drug by a spontaneous cyclization mechanism after cleavage of an enzymatic substrate. It also provides a generic linkage of a drug with a targeting device in a manner set to be triggered by defined enzymatic activity. The system is generic and allows using a variety of drugs, targeting devices, and enzymes by introducing the corresponding substrate as a trigger for drug release in the chemical adaptor. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1853 / 1858
页数:6
相关论文
共 15 条
[1]  
ANDRUSZKIEWICZ R, 1988, POL J CHEM, V62, P257
[2]   A CYTO-TOXIC AGENT CAN BE GENERATED SELECTIVELY AT CANCER SITES [J].
BAGSHAWE, KD ;
SPRINGER, CJ ;
SEARLE, F ;
ANTONIW, P ;
SHARMA, SK ;
MELTON, RG ;
SHERWOOD, RF .
BRITISH JOURNAL OF CANCER, 1988, 58 (06) :700-703
[3]  
de Groot FMH, 2001, CURR MED CHEM, V8, P1093
[4]   A chemical adaptor system designed to link a tumor-targeting device with a prodrug and an enzymatic trigger [J].
Gopin, A ;
Pessah, N ;
Shamis, M ;
Rader, C ;
Shabat, D .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (03) :327-+
[5]  
Grether U, 2001, CHEM-EUR J, V7, P959, DOI 10.1002/1521-3765(20010302)7:5<959::AID-CHEM959>3.3.CO
[6]  
2-B
[7]   ON THE MECHANISM OF TOPOISOMERASE-I INHIBITION BY CAMPTOTHECIN - EVIDENCE FOR BINDING TO AN ENZYME DNA COMPLEX [J].
HERTZBERG, RP ;
CARANFA, MJ ;
HECHT, SM .
BIOCHEMISTRY, 1989, 28 (11) :4629-4638
[8]  
HSIANG YH, 1989, CANCER RES, V49, P4385
[9]   Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review [J].
Maeda, H ;
Wu, J ;
Sawa, T ;
Matsumura, Y ;
Hori, K .
JOURNAL OF CONTROLLED RELEASE, 2000, 65 (1-2) :271-284
[10]   Improved chemical strategies for the targeted therapy of cancer [J].
Maison, W ;
Frangioni, JV .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (39) :4726-4728