Synthesis and HSA binding characterisation of the water soluble 7-succinylpaclitaxel

Eur J Med Chem. 2003 Apr;38(4):383-9. doi: 10.1016/s0223-5234(03)00043-6.

Abstract

A water soluble paclitaxel analogue, the 7-hemisuccinylpaclitaxel, was synthesised and its binding to human serum albumin (HSA) was characterised by difference circular dichroism and optical biosensor methodologies. The carboxylate group was introduced at paclitaxel C-7 position to improve the drug water solubility without significantly changing the biological activity. The paclitaxel analogue showed a relatively low affinity to HSA (3.5x10(4) M(-1)), while no significant interactions were evidenced with selective markers for the most characterised binding sites on the carrier, suggesting a non-selective binding to low affinity binding sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Circular Dichroism / instrumentation
  • Humans
  • Molecular Structure
  • Paclitaxel / analogs & derivatives
  • Paclitaxel / chemical synthesis
  • Paclitaxel / chemistry*
  • Paclitaxel / metabolism
  • Protein Binding
  • Serum Albumin / chemistry
  • Serum Albumin / metabolism*
  • Solubility
  • Time Factors
  • Water / chemistry*

Substances

  • 7-succinylpaclitaxel
  • Serum Albumin
  • Water
  • Paclitaxel