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Preparation of magnetic resonance contrast agents activated by β-galactosidase

Nature Protocols volume 3, pages 341–350 (2008)Cite this article

Abstract

The preparation of β-EgadMe and α-EgadMe, magnetic resonance (MR) contrast agents that can be used for in vivo detection of β-galactosidase, is described. Diastereomerically pure β-EgadMe can be synthesized by kinetically resolving the starting material as described in Step 1. The total time for the preparation of the racemic mixture of β-EgadMe is about 8 d, and the total time for an diastereomerically resolved agent is about 9 d. The final metallated agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5–10) indefinitely. Diastereomerically pure α-EgadMe can be prepared by beginning the synthesis with enantiomerically pure bromopropionic acid. The total time for the preparation of racemic α-EgadMe or diastereomerically pure α-EgadMe is about 8 d. The final metallated agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5–10) indefinitely.

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Figure 1: MR contrast agent, β-EgadMe.
Figure 2
Figure 3: Kinetic resolution of propylene oxide using Jacobsen's catalyst.
Figure 4: Fluorescence HPLC trace of isolated β-EgadMe.

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Authors and Affiliations

  1. Department of Chemistry, Department of Biochemistry and Molecular and Cell Biology, Department of Neurobiology and Physiology, Department of Radiology, Northwestern University, Evanston, 60201, Illinois, USA

    Lauren M Urbanczyk-Pearson & Thomas J Meade

Authors
  1. Lauren M Urbanczyk-Pearson
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  2. Thomas J Meade
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Correspondence to Thomas J Meade.

Supplementary information

Supplementary Fig. 1

Proposed mechanisms of the enzymatic transition of β-EgadMe and α-EgadMe from weak to strong relaxivity states (PDF 97 kb)

Supplementary Fig. 2

MR images of β-EgadMe exposed to heat-treated β-galactosidase (left) and active β-glactosidase (right) (PDF 63 kb)

Supplementary Fig. 3

MRI detection of regions positive for β-galactosidase within a single living Xenopus laevis embryo. (PDF 88 kb)

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Urbanczyk-Pearson, L., Meade, T. Preparation of magnetic resonance contrast agents activated by β-galactosidase. Nat Protoc 3, 341–350 (2008). https://doi.org/10.1038/nprot.2007.529

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