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Self-Immolative Activation of ?-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.


ABSTRACT: Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing ?-galactosidase (?-gal). We investigated two molecular architectures to create agents that detect ?-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 ?-gal.

SUBMITTER: Lilley LM 

PROVIDER: S-EPMC6923588 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Self-Immolative Activation of β-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.

Lilley Laura M LM   Kamper Sarah S   Caldwell Michael M   Chia Zer Keen ZK   Ballweg David D   Vistain Luke L   Krimmel Jeffrey J   Mills Teresa Anne TA   MacRenaris Keith K   Lee Paul P   Waters Emily Alexandria EA   Meade Thomas J TJ  

Angewandte Chemie (International ed. in English) 20191121 1


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<sup>III</sup> . 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  ...[more]

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