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. Epub 2006 Mar 2.

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.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Blood-Brain Barrier
  • Carrier Proteins / chemistry*
  • Cell Line, Tumor
  • Cell-Penetrating Peptides
  • Drug Resistance, Multiple
  • Half-Life
  • Humans
  • Molecular Sequence Data
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacokinetics
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Carrier Proteins
  • Cell-Penetrating Peptides
  • penetratin
  • Paclitaxel