Complete Generation of a ¹²⁹Xe Biosensor on the Solid Support by Systematic Backbone Assembly.

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Molecular Imaging

Background:

• Xenon biosensors are valuable tools for molecular imaging.
• Current methods often involve complex solution-phase synthesis steps.
• Efficient solid-phase synthesis is needed to advance biosensor development.

Purpose of the Study:

• To develop a robust solid-phase synthesis strategy for xenon biosensors.
• To integrate xenon host molecules directly into peptide constructs.
• To evaluate the performance of the synthesized biosensors.

Main Methods:

• Solid-phase synthesis utilizing a modified CryA-da host.
• Optimization of coupling procedures and reagent stoichiometry.
• Characterization of the synthesized biosensor using NMR and MRI.

Main Results:

• A novel solid-phase synthesis strategy for xenon biosensors was successfully established.
• The CryA-da host was efficiently integrated into the peptide backbone on a solid support.
• The synthesized biosensor demonstrated effective NMR (CEST response) and MRI contrast.

Conclusions:

• Solid-phase synthesis offers a streamlined approach for creating xenon biosensors.
• The developed method avoids complex purification steps and side reactions.
• This advancement facilitates the broader application of xenon biosensors in molecular imaging.