Journal
BIOCONJUGATE CHEMISTRY
Volume 20, Issue 2, Pages 390-396Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc800429q
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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.
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