Development of Protein-Binding Bifunctional Linkers for a New Generation of Dual-Acting Prodrugs

被引：45

作者：

Abu Ajaj, Khalid ^{[1
]}

Biniossek, Martin L. ^{[2
]}

Kratz, Felix ^{[1
]}

机构：

[1] Tumor Biol Ctr, D-79106 Freiburg, Germany

[2] Zentrum Biochem & Mol Zellforsch, Inst Mol Med & Cell Res, D-79104 Freiburg, Germany

来源：

BIOCONJUGATE CHEMISTRY | 2009年 / 20卷 / 02期

关键词：

PROSTATE-SPECIFIC ANTIGEN; ENDOGENOUS SERUM-ALBUMIN; METASTATIC BREAST-CANCER; ANTITUMOR EFFICACY; CATHEPSIN-B; IN-VITRO; CLINICAL-TRIALS; PHASE-I; DOXORUBICIN; PACLITAXEL;

D O I：

10.1021/bc800429q

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The aim of this work was to develop a new bifunctional maleimide linker for the development of dual-acting prodrugs that incorporate two pharmaceutically different anticancer agents independently bound by enzymatically cleavable substrates. The linker consists of a carboxyl group in one arm and an activated 1,6-self-immolative para-aminobenzyloxycarbonyl spacer together with a cathepsin B cleavable dipeptide Phe-Lys in the other. Aided with this linker, we have prepared a thiol-binding prodrug that contains the anticancer drugs doxorubicin and paclitaxel. Bound to the cysteine-34 position of albumin, it was cleaved efficiently by cathepsin B releasing the free drugs.

引用

收藏

页码：390 / 396

页数：7

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