Design and synthesis of paclitaxel conjugated with an ErbB2-recognizing peptide, EC-1

Biopolymers. 2007 Nov;87(4):225-30. doi: 10.1002/bip.20828.

Abstract

The selective delivery of therapeutic agents to receptors overexpressed in cancer cells without harming the rest of the body is a major challenge in clinical oncology today. In this study, we report the design and synthesis of paclitaxel (PTX) conjugated with an erbB2-recognizing peptide (EC-1). The cyclic peptide EC-1 specifically binds to the extracellular domain of ErbB2 and selectively inhibits proliferation of breast cancer cells overexpressing ErbB2. PTX is a potent antitumor agent commonly used in the treatment of advanced metastatic breast cancer, yet patients have to suffer some side effects caused by its systemic toxicity. The aim of our conjugate is to specifically deliver antitumor agent PTX to breast cancer cells that overexpress oncogenic ErbB2 with the purpose to reduce toxicity and enhance selective killing of cancer cells. In this study, a concise and efficient synthetic route for the preparation of the PTX-EC-1 conjugate has been developed in 6% overall yield. This synthetic approach provides a general method for conjugating a highly functionalized and disulfide-bridge containing cyclopeptide to Taxol or other antitumor agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Drug Delivery Systems*
  • Drug Design*
  • Female
  • Humans
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemical synthesis
  • Paclitaxel / metabolism
  • Paclitaxel / therapeutic use
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / therapeutic use*
  • Receptor, ErbB-2 / metabolism*

Substances

  • Peptides, Cyclic
  • paclitaxel-EC-1 conjugate
  • Receptor, ErbB-2
  • Paclitaxel