A theranostic abscisic acid-based molecular glue

Molecular glues, capable of selectively controlling the interactions between specific pairs or groups of proteins and the associated downstream effects, have become a promising strategy for manipulating cellular functions and developing novel therapies for human diseases. Theranostics with both diag...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2023-03, Vol.14 (12), p.3377-3384
Main Authors: Chen, Jing, Nguyen, Huong T. X, Yang, Ming, Zeng, Fangxun, Xu, Hang, Liang, Fu-Sen, Wang, Wei
Format: Article
Language:English
Subjects:
Abscisic acid
Active control
Biomedical materials
Chemistry
Gene expression
Glues
Ligands
Proteins
Sensitivity enhancement
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Summary:Molecular glues, capable of selectively controlling the interactions between specific pairs or groups of proteins and the associated downstream effects, have become a promising strategy for manipulating cellular functions and developing novel therapies for human diseases. Theranostics with both diagnostic and therapeutic capabilities acting at disease sites has become a powerful tool to achieve both functions simultaneously with high precision. To selectively activate molecular glues at the desired site and monitor the activation signals at the same time, here we report an unprecedented theranostic modular molecular glue platform integrating signal sensing/reporting and chemically induced proximity (CIP) strategies. We have demonstrated for the first time the integration of imaging and activation capacity with a molecular glue on the same platform to create a theranostic molecular glue. A theranostic molecular glue ABA-Fe( ii )-F1 was rationally designed by conjugating a NIR fluorophore dicyanomethylene-4 H -pyran (DCM) with a CIP inducer abscisic acid (ABA) using a unique carbamoyl oxime linker. We have also engineered a new version of ABA-CIP with an enhanced ligand-responding sensitivity. We have validated that the theranostic molecular glue can sense Fe 2+ and produce turn-on NIR fluorescence for monitoring as well as releasing the active inducer ligand to control cellular functions including gene expression and protein translocation. This novel molecular glue strategy paves the way to building a new class of molecular glues with theranostic capacity for research and biomedical applications. A theranostic ABA-based molecular glue, capable of sensing Fe( ii ) and triggering the release of ABA and NIR fluorophores, has been developed for spatiotemporal monitoring and manipulating cellular functions.
ISSN:2041-6520
2041-6539
DOI:10.1039/d2sc06995d