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Researchers developed a novel theranostic molecular glue platform that combines diagnostic imaging and therapeutic activation. This innovative system allows for targeted control of cellular functions and real-time monitoring of glue activation, advancing precision medicine.

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Area of Science:

  • Biochemistry
  • Chemical Biology
  • Molecular Medicine

Background:

  • Molecular glues offer targeted control over protein interactions for therapeutic development.
  • Theranostics integrate diagnostic and therapeutic functions for precise disease site targeting.
  • Existing molecular glues lack integrated signaling and activation monitoring capabilities.

Purpose of the Study:

  • To develop an unprecedented theranostic molecular glue platform.
  • To integrate signal sensing/reporting with chemically induced proximity (CIP) strategies.
  • To create a molecular glue with simultaneous imaging and activation capacities.

Main Methods:

  • Rational design of a theranostic molecular glue (ABA-Fe(ii)-F1) by conjugating a NIR fluorophore (DCM) with a CIP inducer (abscisic acid, ABA) via a carbamoyl oxime linker.
  • Engineering a novel ABA-CIP with enhanced ligand-responding sensitivity.
  • Validating the platform's ability to sense Fe2+ and trigger NIR fluorescence and release of the active inducer ligand.

Main Results:

  • Demonstrated the first integration of imaging and activation in a single molecular glue platform.
  • The theranostic molecular glue successfully sensed Fe2+ ions, producing a turn-on NIR fluorescence signal for monitoring.
  • The platform effectively released the active inducer ligand to control cellular functions, including gene expression and protein translocation.

Conclusions:

  • The developed theranostic molecular glue platform enables simultaneous monitoring and targeted activation of molecular glues.
  • This novel strategy provides a new class of molecular glues with theranostic capabilities.
  • The platform holds significant potential for advancing biomedical research and therapeutic applications.