Cyclic Peptide High-Entropy Noncovalent Glass

Abstract

The design and exploration of stable noncovalent glass based on biomolecules are paramount for the sustainable development of human society. Cyclic peptides (CPs) with remarkable structural rigidity and decent resistance to enzymatic degradation can serve as promising glass formers. However, the potent crystallization tendency hinders their potential in glass construction. Herein, we engineered a series of CP glasses with tunable glass transition behaviors by modulating the conformational complexity of CP clusters. The increasing conformational entropy of the supercooled liquid of CPs compared to their crystalline counterparts is fundamental to the formation of CP noncovalent glass. By incorporating multicomponent CPs, the formation of high-entropy CP (HECP) glass is facilitated, which in turn inhibits the crystallization and decomposition of individual CPs. This process ultimately enhances the stability of CP noncovalent glass. Such HECP glass exhibits enhanced mechanical properties compared to individual CP glass due to the promoted connectivity within the glass network. These findings offer a promising paradigm for designing and developing stable noncovalent glass based on naturally derived biomolecules and advancing their application in pharmaceutical formulations and smart materials.

Peptide Self-assembly: From Ordered to Disordered

“…(C) Experimental evidence and schematic illustration showing the concept of high-entropy cyclic peptide glass. Reproduced with permission from ref . Copyright 2023 Research Square.…”

“…Nevertheless, their inherent rigidity often leads to crystallization, challenging glass construction. To overcome this, we engineered noncovalent glasses using pure CPs by modulating CP cluster conformation complexity . Notably, CPs including Cyclo­(-Phe-Pro) (CFP), Cyclo­(-Pro-Tyr) (CPY), Cyclo­(-Trp-Tyr) (CWY), and Cyclo­(-Trp-Trp) (CWW), defined as Type I molecules, can form stable glasses through direct melting-quenching.…”