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Synthesis and biological activity of conjugates between paclitaxel and the cell delivery vector penetratin
Shudong Wang1, Nikolai Z Zhelev, Susan Duff
1Cyclacel Limited, James Lindsay Place, Dundee DD1 5JJ, Scotland, UK. shudong.wang@nottingham.ac.uk
Abstract:
Synthesis of paclitaxel-penetratin (pAntp) constructs, in which the 2'- or 7-position of paclitaxel was used as the attachment site for linker connecting the drug and peptide moieties, is described. Paclitaxel-2'-pAntp[43-58]-NH(2)3b and paclitaxel-2'-pAntp[52-58]-NH(2)3c showed excellent antitumour activity against human lung and breast cancer cell lines. These conjugates were highly soluble and stable with a half-life of >8h under cell culture conditions. The drug-peptide conjugates may be therapeutically useful due to improved pharmaceutical properties.
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