Synthesis and biological activity of conjugates between paclitaxel and the cell delivery vector penetratin

  • Bioorg Med Chem Lett. 2006 May 15;16(10):2628-31. doi: 10.1016/j.bmcl.2006.02.035.
Shudong Wang  1 ,  Nikolai Z Zhelev ,  Susan Duff ,  Peter M Fischer
Affiliations
  • 1. Cyclacel Limited, James Lindsay Place, Dundee DD1 5JJ, Scotland, UK. [email protected]
PMID: 16513344 DOI: 10.1016/j.bmcl.2006.02.035
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.