A thiol-selective and acid-stable protein modification strategy using an electron-deficient yne reagent

Area of Science:

• Bioconjugation Chemistry
• Chemical Biology
• Cancer Research

Background:

• Protein modification is crucial for developing targeted therapies and diagnostics.
• Existing methods often face challenges with selectivity, stability, and reaction kinetics.
• The development of efficient and specific bioconjugation strategies remains a key area of research.

Purpose of the Study:

• To develop a robust protein modification strategy utilizing thiol-yne click chemistry.
• To create highly stable antibody conjugates for biological applications.
• To enable the specific imaging of Programmed Death-Ligand 1 (PD-L1) in cancer cells.

Main Methods:

• Employed an electron-deficient yne reagent for thiol-yne click reactions.
• Conjugated immunoglobulin G (IgG) antibodies with an indole-derived fluorophore.
• Utilized the developed strategy for the selective labeling of proteins.

Main Results:

• Achieved highly selective conjugation towards thiol groups.
• Demonstrated rapid reaction kinetics for efficient labeling.
• Generated antibody conjugates with superior acid stability.
• Successfully imaged PD-L1 in cancer cells using the developed fluorescently labeled IgG.

Conclusions:

• The developed thiol-yne click reaction offers a powerful and selective method for protein modification.
• This strategy yields conjugates with enhanced stability, suitable for demanding biological applications.
• The successful imaging of PD-L1 highlights the potential of this approach in cancer diagnostics and research.