The enzyme-instructed assembly of the core of yeast prion Sup35 to form supramolecular hydrogels

Abstract

Based on the self-assembly capability of the core segment (GNNQQNY) of yeast prion Sup35, we design and synthesis a series of structurally related precursors for enzymatic formation of hydrogels. We found that, with the catalysis of alkaline phosphatase, the precursor becomes a hydrogelator that self-assembles in water to form nanofibers with an average width less than ten nanometers. Interestingly, the introduction of amyloid segment into a cytotoxic precursor (N’ffyp: D-1P) is able to abrogate the cytotoxicity of the precursor, making the resulting peptide to be cell compatible. This work contributes a new insight to the use of enzyme to form cell compatible hydrogels of peptides cross-β spine.

Controlling the Self-Assembly of Biomolecules into Functional Nanomaterials through Internal Interactions and External Stimulations: A Review

“…Besides biopolymers, the self-assembly of other biomolecules, such as proteins, peptides, and DNA, could be driven by enzymes [ 148 , 149 , 150 , 151 ]. Previously, Xu’s group used the enzyme-instructed self-assembly (EISA) approach to prepared a few supramolecular nanostructures, such as nanofibers and hydrogels [ 13 , 152 , 153 , 154 ]. For example, they designed a series of structural precursors based on the peptide GNNQQNY sequence of the yeast prion Sup35, which can self-assemble to form supramolecular hydrogels induced by alkaline phosphatase in water ( Figure 11 b) [ 152 ].…”

“…Previously, Xu’s group used the enzyme-instructed self-assembly (EISA) approach to prepared a few supramolecular nanostructures, such as nanofibers and hydrogels [ 13 , 152 , 153 , 154 ]. For example, they designed a series of structural precursors based on the peptide GNNQQNY sequence of the yeast prion Sup35, which can self-assemble to form supramolecular hydrogels induced by alkaline phosphatase in water ( Figure 11 b) [ 152 ]. In another study [ 155 ], they investigated the enzyme-induced in-situ self-assembly of C-terminal methylated phosphotetrapeptide (pTP-Me) into PNFs.…”

“…( b ) Alkaline phosphatase (ALP)-mediated formation of a peptide hydrogel. Reprinted with permission from [ 152 ]. Copyright 2016 The Royal Society of Chemistry.…”

Self-Assembled Bio-Nanomaterials

“…Besides biopolymers, the self-assembly of other biomolecules, such as proteins, peptides, and DNA, could be driven by enzymes [148][149][150][151]. Previously, Xu's group used the enzyme-instructed self-assembly (EISA) approach to prepared a few supramolecular nanostructures, such as nanofibers and hydrogels [13,[152][153][154]. For example, they designed a series of structural precursors based on the peptide GNNQQNY sequence of the yeast prion Sup35, which can self-assemble to form supramolecular hydrogels induced by alkaline phosphatase in water ( Figure 11b) [152].…”

“…Previously, Xu's group used the enzyme-instructed self-assembly (EISA) approach to prepared a few supramolecular nanostructures, such as nanofibers and hydrogels [13,[152][153][154]. For example, they designed a series of structural precursors based on the peptide GNNQQNY sequence of the yeast prion Sup35, which can self-assemble to form supramolecular hydrogels induced by alkaline phosphatase in water ( Figure 11b) [152]. In another study [155], they investigated the enzyme-induced in-situ self-assembly of C-terminal methylated phosphotetrapeptide (pTP-Me) into PNFs.…”