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.
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.
Wardle
Nick J
NJ
Institute for Health Research and Policy, Tower Building, London Metropolitan University, and Hammersmith Hospital, London, UK.
Herlihy
Amy H
AH
So
Po-Wah
PW
Bell
Jimmy D
JD
Bligh
S W Annie
SW
D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D011522:Protons
C521783:1-(2-(beta,D-galactopyranosyloxy)ethyl)-7-(1-carboxy-3-(4-aminophenyl)propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D011522:Protons; D005682:Gadolinium