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

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]-NH23b and paclitaxel–2′-pAntp[52–58]-NH23c showed excellent antitumour activity against human lung and breast cancer cell lines. These conjugates were highly soluble and stable with a half-life of >8 h under cell culture conditions. The drug–peptide conjugates may be therapeutically useful due to improved pharmaceutical properties.

Graphical abstractSynthesis of paclitaxel–penetratin (pAntp) constructs, in which the 2′- or 7-position of paclitaxel was used as the attachment site for linkers connecting the drug and peptide moieties, is described. Conjugates 3b and 3c were highly soluble and stable with a half-life of >8 h under cell culture conditions. Their antitumour activities were determined.Figure optionsDownload full-size imageDownload as PowerPoint slide