title: Synthesis and biological activity of conjugates between paclitaxel and the cell delivery vector penetratin.
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.
authors.affiliation: Cyclacel Limited, James Lindsay Place, Dundee DD1 5JJ, Scotland, UK. shudong.wang@nottingham.ac.uk
authors.forename: Shudong
authors.initials: S
authors.lastname: Wang
authors.forename: Nikolai Z
authors.initials: NZ
authors.lastname: Zhelev
authors.forename: Susan
authors.initials: S
authors.lastname: Duff
authors.forename: Peter M
authors.initials: PM
authors.lastname: Fischer
mesh_terms: D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier; D002352:Carrier Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides; D018432:Drug Resistance, Multiple; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; C414409:penetratin; D017239:Paclitaxel