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Updated: May 27, 2025
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Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
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Stabilization of a protein by a single halogen-based aromatic amplifier
Krystel El Hage1,2, Balamurugan Dhayalan3, Yen-Shan Chen3
1Department of Chemistry, University of Basel, Basel, Switzerland.
Protein Science : a Publication of the Protein Society
|February 19, 2025
Summary
Halogenation stabilizes insulin by modifying electrostatic interactions. Ortho-substituted analogs show enhanced stability and retain biological activity, improving pharmaceutical formulations.
Area of Science:
- Protein Engineering
- Medicinal Chemistry
- Biophysics
Background:
- Halogenation is a strategy for protein design.
- Understanding electrostatic interactions is key to protein stability.
Purpose of the Study:
- Investigate halogenation's utility in protein design.
- Enhance the stability of pharmaceutical insulin.
Main Methods:
- Quantitative atomistic simulations.
- Experimental validation using insulin analogs.
- Assays for thermodynamic stability, receptor binding, and fibrillation.
Main Results:
- Ortho-halogenation of phenylalanine B24 stabilized insulin (ΔΔGu = -0.5 to -1.0 kcal/mol).
- Ortho-analogs retained biological activity in cellular and animal models.
- Enhanced resistance to fibrillation was observed above room temperature.
Conclusions:
- Regiospecific halogenation effectively stabilizes insulin.
- This approach can improve the shelf-life of insulin formulations.
- Potential applications for other therapeutic proteins and vaccines.
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