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 (T cp) 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.

Chirality-Regulated Clusteroluminescence in Polypeptides

“…47 L 100 shows negative peaks at 208 and 222 nm as well as a positive peak at 195 nm (Figure 4b), proving the formation of a typical α-helical conformation. 48 The helical content of polypeptides can be assigned to the peak intensity at 222 nm. 48 Then, the substitution of monomers with opposite chirality leads to a decreasing CD signal (L 75 D 25 ) until there is no signal and a disordered random coil as L 50 D 50 (Figure 4b).…”

“…48 The helical content of polypeptides can be assigned to the peak intensity at 222 nm. 48 Then, the substitution of monomers with opposite chirality leads to a decreasing CD signal (L 75 D 25 ) until there is no signal and a disordered random coil as L 50 D 50 (Figure 4b). 38 Moreover, positive peaks appear when D residues are more abundant than L ones in polypeptides (L 25 D 75 ).…”

“…The resolution of the CD measurement is strongly limited by the UV absorbance of the THF; therefore, the secondary structure of polypeptides in solution was investigated in hexafluoroisopropanol (HFIP) . L 100 shows negative peaks at 208 and 222 nm as well as a positive peak at 195 nm (Figure b), proving the formation of a typical α-helical conformation . The helical content of polypeptides can be assigned to the peak intensity at 222 nm .…”

Activation of Upper Critical Solution Temperature Behaviors of Zwitterionic Poly(l-methionine-g-poly(sulfobetaine methacrylate)m) with a Bottlebrush Structure

“…It is assumed that the positive and negative charges in the side chain have the capacity to form both intramolecular and intermolecular electrostatic interactions . Hence, in this work, VT-NMR is applied to explore the variation of the local chemical environments of these characteristic protons in response to temperature changes. , …”

“…The selection of appropriate macromolecular initiators via the grafting-from strategy is critical to preparing bottlebrush polymers. Researchers have chosen synthetic polypeptides as the main chain to avoid potential biocompatibility issues caused by the carbon-based backbone. − Bromo-functionalized poly­( l -lysine) has been used as the ATRP macroinitiator to produce polypeptide bottlebrushes . Subsequently, the polypeptide side chains were chemically modified for subsequent reactions via the postpolymerization modification route. , The alkylation of l -methionine (Met) residues has been expanded to a wide range of functional groups on polypeptides. − In our previous work, alkylation of poly­( l -methionine) (PMet) showed high reaction efficiency under mild conditions, allowing for the introduction of functional trehalose groups via the subsequent click reaction …”