Structure of a 129Xe-cryptophane biosensor complexed with human carbonic anhydrase II
Julie A Aaron1, Jennifer M Chambers, Kevin M Jude
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
Journal of the American Chemical Society
|May 9, 2008
Summary
Cryptophanes, xenon-encapsulating molecules, can guide xenon atoms for enhanced medical imaging. Their structure reveals minimal protein interaction, improving sensitivity for 129Xe NMR spectroscopy.
Area of Science:
- Supramolecular Chemistry
- Biophysical Chemistry
- Medical Imaging
Background:
- Cryptophanes are xenon-binding molecules with potential as nuclear magnetic resonance (NMR) imaging agents.
- Targeted delivery of xenon to specific biological sites is crucial for effective NMR imaging.
- Understanding the interaction between cryptophanes and biological targets is key to optimizing their use.
Purpose of the Study:
- To determine the crystal structure of a cryptophane complexed with human carbonic anhydrase II.
- To elucidate how encapsulated xenon atoms are directed to a specific biological target.
- To assess the interaction between the cryptophane cage and the protein surface.
Main Methods:
- X-ray crystallography at 1.70 Å resolution.
- Complex formation between a cryptophane-derivatized benezenesulfonamide and human carbonic anhydrase II.
- Analysis of binding interactions and structural features.
Main Results:
- The crystal structure reveals the precise orientation of the cryptophane-derivatized benezenesulfonamide within the active site of human carbonic anhydrase II.
- The encapsulated xenon atom is shown to be directed towards a specific biological target.
- The cryptophane cage exhibits minimal strong interactions with the protein surface.
Conclusions:
- The structural data provides a molecular basis for the targeted delivery of xenon using cryptophane probes.
- The limited interaction of the cryptophane cage with the protein surface is a favorable characteristic for enhancing NMR signal sensitivity.
- These findings support the development of cryptophanes as sensitive probes for 129Xe NMR imaging of biological systems.
