Title
Comparative Study of Protein Aggregation Arrest by Zwitterionic Polysulfobetaines: Using Contrasting Raft Agents
Author
Neha Sharma, Robin Rajan, Sparsh Makhaik, Kazuaki Matsumura
Year
2019
Journal
ACS Omega
Abstract
Protein aggregation has caused limitations in the study and development of protein-based biopharmaceuticals. We prepared different polysulfobetaine (poly-SPB) polymers via reversible addition fragmentation chain transfer (RAFT) polymerization. These polymers exhibited high efficiency in modulation of protein aggregation. We synthesized polysulfobetaines using two different RAFT agents, and analyzed the aggregation profile of lysozyme and insulin. In poly-SPBs, existence of a hydrophobic RAFT agent resulted in visible enhancement of the residual enzymatic activity of lysozyme, whereas it remained unaffected by the hydrophilic RAFT agent. In addition, these polymers resulted in significant suppression in the aggregation of insulin. Increase in the molecular weight of the polymer caused higher efficiency to perpetuate enzymatic activity of lysozyme upon thermal denaturation. The polymers arrested the formation of amyloid like fibrils of lysozyme and insulin, thus indicating their potential to inhibit aggregation. The results unambiguously demonstrate the importance of polysulfobetaine moiety and hydrophobicity in protein aggregation inhibition. This study gives insight into the protein aggregation inhibition by zwitterionic polymers, which have a potential to be developed as aggregation inhibitors in the future.
Instrument
V-670, FP-8600
Keywords
Absorption, Turbidity, Aggregation, Polymers, Fluorescence, Protein structure, Biochemistry