Secondary Structure-Governed Phase Separation Behavior in Glutamate-Based Polypeptides.

Abstract

The phase separation behavior of biomacromolecules plays a key role in the fields of biology and medicine. In this work, we gain a deep insight into how the primary and secondary structures govern and regulate the phase separation behavior of polypeptides. To this end, we synthesized a series of polypeptides with tailorable hydroxyl-containing side chains. The secondary structure of polypeptides can be modulated by the local chemical environment and content of side chains. Interestingly, these polypeptides with different helical contents exhibited upper critical solution temperature behavior with marked differences in the cloud point temperature (Tcp) and the width of hysteresis. The phase transition temperature is highly relevant to the content of secondary structure and interchain interactions of polypeptides. The aggregation/deaggregation and the transition of secondary structure are completely reversible during heating-cooling cycles. Much to our surprise, the recovery rate of the α-helical structure governs the width of hysteresis. This work establishes the structure-property relationship between the secondary structure and phase separation behavior of the polypeptide and delivers new insight into the rational design of peptide-based materials with tailor-made phase separation behavior.