As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant β-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.

Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.

Self-adaptive bulk/surface engineering of Bi O Br towards enhanced photocatalysis: Current status and future challenges

Vitiligo, a common skin disease that seriously affects 0.5-2.0% of the worldwide population, lacks approved therapeutics due to a wide range of adverse side effects. As a key regulator of skin pigmentation, MC1R may be an effective therapeutic target for vitiligo. Herein, we report an MC1R peptide agonist that directly self-assembles into nanofibrils that form a hydrogel matrix under normal physiological conditions. This hydrogel exhibits higher stability than free peptides, sustained release, rapid recovery from shear-thinning, and resistance to enzymatic proteolysis. Furthermore, this peptidal MC1R agonist upregulates tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) to stimulate melanin synthesis. More importantly, MC1R agonist hydrogel promotes skin pigmentation in mice more potently than free MC1R agonist. This study supports the development of this MC1R agonist hydrogel as a promising pharmacological intervention for vitiligo.

MC1R Peptide Agonist Self-Assembles into a Hydrogel That Promotes Skin Pigmentation for Treating Vitiligo.

Dynamic-responsive self-assembly is the process of ordered supramolecular structure formation or reversible decomposition from building blocks. This process is driven by non-covalent interactions based on complex stimulus-responsive systems comprising different components within a microenvironment. Furthermore, stimuli-responsive assembly-disassembly is an intrinsic interaction process in organisms, indispensable in maintaining life activities and functions. However, the dynamic interactions between dynamically responsive nano-drug systems (DRNSs) and biological systems remain unpredictable, which are a challenge for the precisely targeted therapy and controlled drug release of DRNSs in vivo. This review highlights novel self-assembling peptide-based nano-drug systems and their biological interactions. By precisely controlling the shape and size of self-assembled peptide nanomaterials, biologically simulated components with diverse biological functions and precise transport at the subcellular level can be achieved. We have also summarized the limitations and challenges of responsive self-assembling peptide nanomaterials in clinical translation. Additionally, we have discussed the future perspectives of supramolecular therapeutics using signaling molecule gradient concentrations and efficiencies and highlighted the direction for developing clinically translatable smart nanomedicines. 

Dynamic responsiveness of self‐assembling peptide‐based nano‐drug systems

Cysteine redox chemistry is widely used in nature to direct protein assembly, and in recent years it has inspired chemists to design self-assembling peptides too. In this concise review, we describe the progress in the field focusing on the recent advancements that make use of Cys thiol–disulfide redox chemistry to modulate hydrogelation of various peptide classes.

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Cysteine Redox Chemistry in Peptide Self-Assembly to Modulate Hydrogelation

Disulfide bond formation is a common mechanism for regulating conformational changes in proteins during oxidative folding. Despite extensive studies of the use of multiple disulfide bonds to constrain peptide conformation, few studies have explored their usage in developing self-assembling peptides. Herein, we report that a thiol-rich peptide could fold into an amphiphilic β-hairpin conformation through the formation of two hetero-disulfide bonds upon oxidation, subsequently self-assembling into a mechanically rigid hydrogel. Breaking disulfide bonds under reductive condition, the hydrogel exhibited a transition from hydrogel to solution. Molecular simulation revealed that intermolecular interaction between two tryptophan residues was indispensable for hydrogelation. This work is the first case of the use of multiple disulfide bonds to control conformational change and self-assembly, and provides a cell-compatible hydrogel material for potential biomedical application.

Mingshui Wang

Papers

Redox-Regulated Conformational Change of Disulfide-Rich Assembling Peptides.