1. Self-Immolative Activation of β-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.
- Author
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Lilley LM, Kamper S, Caldwell M, Chia ZK, Ballweg D, Vistain L, Krimmel J, Mills TA, MacRenaris K, Lee P, Waters EA, and Meade TJ
- Subjects
- Animals, Disease Models, Animal, Mice, Molecular Structure, Magnetic Resonance Imaging methods, beta-Galactosidase metabolism
- Abstract
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 Gd
III . 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., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2020
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