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Area of Science:

  • Biochemistry
  • Biophysics
  • Medical Imaging

Background:

  • Magnetic resonance imaging (MRI) contrast agents currently lack analyte-responsiveness.
  • Disease biomarkers, such as glutamine (Gln) in tumors, offer potential for targeted imaging.
  • Switchable artificial metalloproteins (swArMs) can be engineered for analyte-responsive functions.

Purpose of the Study:

  • To develop a proof-of-concept analyte-responsive MRI contrast agent.
  • To investigate the Gln-binding-induced signal changes in swArMs.
  • To optimize swArM design for enhanced MRI contrast.

Main Methods:

  • Engineered swArMs with MRI-active metals (Gd3+, Dy3+) and various ligands.
  • Characterized Gln-binding affinity using isothermal titration calorimetry.
  • Verified conformational changes with circular dichroism and determined structures via X-ray diffraction.

Main Results:

  • swArMs demonstrated Gln-responsive MRI signal changes.
  • A ~60% increase in T2 relaxivity was observed upon Gln binding.
  • Structural analysis revealed metallocofactor interactions modulated by Gln binding.

Conclusions:

  • Developed a novel platform for analyte-responsive MRI contrast agents.
  • Demonstrated the potential of swArMs for detecting disease biomarkers like glutamine.
  • Opened new avenues for targeted and responsive molecular imaging.