Cephalosporin prodrugs of paclitaxel for immunologically specific activation by L-49-sFv-beta-lactamase fusion protein

Bioorg Med Chem Lett. 2003 Feb 10;13(3):539-42. doi: 10.1016/s0960-894x(02)00935-6.

Abstract

Paclitaxel conjugates of 7-phenylacetamidocephalosporanic acid were prepared as prodrugs for site specific activation by targeted beta-lactamase. Immunologically specific activation of the prodrug 5 containing 3,3-dimethyl-4-amino-butyric acid as linker in combination with the fusion protein L-49-sFv-beta-lactamase was demonstrated in vitro on 3677 melanoma cells.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cephalosporins / chemical synthesis*
  • Cephalosporins / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cyclization
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Half-Life
  • Humans
  • Immunoglobulin G / pharmacology*
  • In Vitro Techniques
  • Indicators and Reagents
  • Melanoma, Experimental / drug therapy
  • Paclitaxel / analogs & derivatives
  • Paclitaxel / chemical synthesis*
  • Paclitaxel / pharmacology*
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology*
  • Recombinant Fusion Proteins / chemical synthesis*
  • Recombinant Fusion Proteins / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Cephalosporins
  • Enzyme Inhibitors
  • Immunoglobulin G
  • Indicators and Reagents
  • Prodrugs
  • Recombinant Fusion Proteins
  • beta-Lactamase Inhibitors
  • L49-sFv-beta-lactamase
  • beta-Lactamases
  • Paclitaxel