Stimuli-Responsive Hydrazone/Oxime Ligation for Selective Labeling of Cell Surface Glycoproteins

Area of Science:

• Chemical Biology
• Biomolecular Engineering

Background:

• Precise spatial and temporal control of bioorthogonal reactions is crucial for targeted biomolecular labeling in living systems.
• Existing cell-selective labeling strategies primarily focus on regulating bioorthogonal tag insertion.

Purpose of the Study:

• To develop an alternative strategy for biomolecular labeling by controlling the second stage of the labeling process.
• To achieve stimuli-controlled, selective labeling of cell surface glycoproteins.

Main Methods:

• Utilized controllable hydrazone/oxime ligation for biomolecular labeling.
• Introduced stimuli-responsive protecting groups (photo-, ROS-, and LAP-responsive) to inhibit hydrazide/hydroxylamine reactivity.
• Combined with ketone-based metabolic glycan labeling for cell surface targeting.

Main Results:

• Developed a method to inhibit and restore the reactivity of hydrazides/hydroxylamines using stimuli-responsive protecting groups.
• Demonstrated selective labeling of cell surface glycoproteins in stimuli-rich environments (light, ROS, or LAP).
• Achieved spatial and temporal control over bioorthogonal reactions.

Conclusions:

• The stimuli-controlled hydrazone/oxime ligation strategy offers a novel approach for targeted biomolecular labeling.
• This method enables selective labeling of cell surface glycoproteins under specific environmental stimuli.
• Holds significant promise for applications in chemical biology and controllable tumor targeting.