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.