Self-Immolative Activation of ß-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.
Angew Chem Int Ed Engl
; 59(1): 388-394, 2020 01 02.
Article
em En
| MEDLINE
| ID: mdl-31750611
ABSTRACT
Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing ß-galactosidase (ß-gal). We investigated two molecular architectures to create agents that detect ß-gal activity by modulating the coordination of water to GdIII . The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the GdIII ion. This renders the agent ineffective. We show that one agent in particular (6-C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing ß-gal.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
/
Beta-Galactosidase
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article