Self-Immolative Activation of β-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.
Laura M LilleySarah KamperMichael CaldwellZer Keen ChiaDavid BallwegLuke VistainJeffrey KrimmelTeresa Anne MillsKeith MacRenarisPaul LeeEmily Alexandria WatersThomas J MeadePublished in: Angewandte Chemie (International ed. in English) (2019)
Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-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 β-gal.
Keyphrases
- mouse model
- contrast enhanced
- magnetic resonance
- small molecule
- magnetic resonance imaging
- single molecule
- crispr cas
- energy transfer
- signaling pathway
- computed tomography
- quantum dots
- cancer therapy
- living cells
- atomic force microscopy
- loop mediated isothermal amplification
- label free
- real time pcr
- drug delivery
- fluorescent probe