Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Protein Biochemistry

Background:

• Neutral, water-soluble polymers like poly(ethylene glycol) (PEG) and poly(zwitterions) (pSB) are widely used in biomedical applications due to their presumed low protein binding.
• This low protein binding is a key characteristic for their efficacy in preventing non-specific interactions.

Purpose of the Study:

• To investigate the direct interaction between poly(sulfobetaine) (pSB) and proteins in solution.
• To determine the effect of pSB on protein thermal stability and folding cooperativity.
• To assess whether pSB is universally protein-repellent.

Main Methods:

• Utilized tryptophan fluorescence spectroscopy to analyze changes in protein conformation and local polarity.
• Performed thermal denaturation studies to measure protein melting temperatures and folding cooperativity.
• Examined the interactions of soluble 100 kDa pSB with three structurally distinct proteins.

Main Results:

• Demonstrated direct interaction between soluble pSB and all three tested proteins.
• Observed that pSB reduces protein thermal stability (up to ~1.9 °C per wt%) and increases folding cooperativity (up to ~130 J mol⁻¹ K⁻¹ per wt%).
• Found that the extent of these changes is protein-dependent, with some proteins showing increased stability at high pSB concentrations.

Conclusions:

• Poly(sulfobetaine) (pSB) is not universally protein-repellent.
• pSB can directly interact with proteins, influencing their stability and conformation.
• The effectiveness of pSB in biotechnological applications is dependent on the specific protein interactions involved.