Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its Gd(III) complex

Bioorg Med Chem. 2007 Jul 15;15(14):4714-21. doi: 10.1016/j.bmc.2007.05.004. Epub 2007 May 6.

Abstract

A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of beta-galactosidase, respectively.

MeSH terms

  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Gadolinium / chemistry*
  • Heterocyclic Compounds, 1-Ring / chemical synthesis*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Ligands
  • Molecular Structure
  • Protons

Substances

  • 1-(2-(beta,D-galactopyranosyloxy)ethyl)-7-(1-carboxy-3-(4-aminophenyl)propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane
  • Chelating Agents
  • Heterocyclic Compounds, 1-Ring
  • Ligands
  • Protons
  • Gadolinium