An Exploration of Multiple Component Peptide Assemblies by Enzyme-Instructed Self-Assembly.

Based on the motifs (RNISY (M) and DEEVELILGDT (D)) in the protein crystal structures of Merlin and CRL4, we phosphorylated the tyrosine residue in M and conjugated M to a self-assembling motif to produce a phosphopeptide () and examined enzyme-instructed self-assembly (EISA) of with and without the presence of D (). Our results show that EISA of forms a hydrogel at exceedingly low volume fraction (~ 0.03%) even with the presence of the hydrophilic peptide, .

Enzymatically Forming Intranuclear Peptide Assemblies for Selectively Killing Human Induced Pluripotent Stem Cells.

Tumorigenic risk of undifferentiated human induced pluripotent stem cells (iPSCs), being a major obstacle for clinical application of iPSCs, requires novel approaches for selectively eliminating undifferentiated iPSCs. Here, we show that an l-phosphopentapeptide, upon the dephosphorylation catalyzed by alkaline phosphatase (ALP) overexpressed by iPSCs, rapidly forms intranuclear peptide assemblies made of α-helices to selectively kill iPSCs. The phosphopentapeptide, consisting of four l-leucine residues and a C-terminal l-phosphotyrosine, self-assembles to form micelles/nanoparticles, which transform into peptide nanofibers/nanoribbons after enzymatic dephosphorylation removes the phosphate group from the l-phosphotyrosine.

Heterotypic Supramolecular Hydrogels Formed by Noncovalent Interactions in Inflammasomes.

The advance of structural biology has revealed numerous noncovalent interactions between peptide sequences in protein structures, but such information is less explored for developing peptide materials. Here we report the formation of heterotypic peptide hydrogels by the two binding motifs revealed by the structures of an inflammasome. Specifically, conjugating a self-assembling motif to the positively or negatively charged peptide sequence from the ASCPYD filaments of inflammasome produces the solutions of the peptides.

Enzymatic Noncovalent Synthesis.

Enzymatic reactions and noncovalent (i.e., supramolecular) interactions are two fundamental nongenetic attributes of life.

Enzyme-instructed self-assembly of the stereoisomers of pentapeptides to form biocompatible supramolecular hydrogels.

This article reports enzyme-instructed self-assembly (EISA) of stereoisomers of pentapeptides as a simple approach for generating biocompatible supramolecular hydrogels as potential soft bionanomaterials. Peptide-based supramolecular hydrogels are emerging as a new type of biomaterials. The use of tyrosine phosphate offers a trigger for enzymatic hydrogelation, and the incorporation of D-amino acids can increase the proteolytic stability of peptides.

Enzymatic Noncovalent Synthesis of Supramolecular Soft Matter for Biomedical Applications.

Enzymatic noncovalent synthesis (ENS), a process that integrates enzymatic reactions and supramolecular (i.e., noncovalent) interactions for spatial organization of higher-order molecular assemblies, represents an emerging research area at the interface of physical and biological sciences.