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Rotaxane probes for protease detection by 129Xe hyperCEST NMR.

Clancy C Slack1, Joel A Finbloom2, Keunhong Jeong1

  • 1Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA. mbfrancis@berkeley.edu and Materials Sciences Division, Lawrence Berkeley National Laboratories, Berkeley, CA 94720, USA.

Chemical Communications (Cambridge, England)
|January 4, 2017
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Summary

We developed a novel rotaxane molecule for detecting matrix metalloprotease 2 (MMP-2), an important cancer marker. This new method uses 129Xe hyperCEST NMR to enable protease-responsive imaging in cancer diagnostics.

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Area of Science:

  • Supramolecular Chemistry
  • Chemical Biology
  • Biomedical Imaging

Background:

  • Matrix metalloproteinase 2 (MMP-2) is frequently overexpressed in cancerous tissues, making it a significant biomarker for cancer detection.
  • Current methods for MMP-2 detection can be limited in sensitivity and specificity.
  • Developing novel molecular tools for sensitive and specific MMP-2 detection is crucial for advancing cancer diagnostics.

Purpose of the Study:

  • To develop a novel supramolecular system for the sensitive and specific detection of matrix metalloproteinase 2 (MMP-2) activity.
  • To utilize 129Xe hyperCEST NMR as a detection platform for protease activity.
  • To create a protease-responsive molecular probe for potential cancer imaging applications.

Main Methods:

  • Synthesis of a cyclobis(para-phenylene-22-crown-6) (CB6) based rotaxane incorporating a peptide substrate specific for MMP-2.
  • Utilizing CB6-promoted click chemistry for the efficient synthesis of the rotaxane.
  • Employing 129Xe hyperCEST NMR spectroscopy to monitor the interaction of 129Xe with the CB6 cage upon MMP-2 cleavage.

Main Results:

  • Successful synthesis of the CB6 rotaxane with an embedded MMP-2 recognition sequence.
  • Demonstration that MMP-2 enzymatic activity cleaves the rotaxane, releasing the CB6 cage.
  • Observation of protease-responsive activation of 129Xe@CB6 interactions, indicating successful detection of MMP-2 activity.

Conclusions:

  • The developed CB6 rotaxane serves as an effective molecular probe for MMP-2 activity.
  • 129Xe hyperCEST NMR in conjunction with this rotaxane offers a sensitive method for detecting protease activity.
  • This approach holds promise for the development of new diagnostic tools for cancer detection based on MMP-2 levels.