Polyampholytes and Their Hydrophobic Derivatives as Excipients for Suppressing Protein Aggregation

Abstract

Protein aggregation, which occurs under various physiological conditions, can affect cell function and is a major issue in the field of protein therapeutics. In this study, we developed a polyampholyte composed of ε-poly-l-lysine and succinic anhydride and evaluated its protein protection efficacy. This polymer was able to protect different proteins from thermal stress and its performance significantly exceeded that of previously reported zwitterionic polymers. In addition, we synthesized derivatives with varying degrees of hydrophobicity, which exhibited remarkably enhanced efficiency; thus, the polymer concentration required for protein protection was very low. By facilitating the retention of protein enzymatic activity and stabilizing the higher-order structure, these polymers enabled the protein to maintain its native state, even after being subjected to extreme thermal stress. Thus, such polyampholytes are extremely effective in protecting proteins from extreme stress and may find applications in protein biopharmaceuticals and drug delivery systems.

Modulating the aggregation of human prion protein PrP106–126 by an indole-based cyclometallated palladium complex

“…24–28 To prevent amyloid aggregation, certain natural products, chemical compounds, polymers, nanoparticles, and molecular chaperones that are well-suited to human bodies have been utilised. 29–34 These agents work through non-covalent interactions and oxidative stress that affect how individual amyloid monomers recognize and assemble themselves. The use of metal-based therapeutics as inhibitors of amyloid fibril formation and toxicity to treat NDDs is a rapidly evolving field.…”