Systems chemistry of peptide-assemblies for biochemical transformations

Abstract

The review focuses on the recent developments on diverse sets of complex enzymatic transformations by utilizing minimal peptide based self-assembled systems. It further attempts to provide a broad perspective for potentially programming functionality via rational selection of amino acid sequences, leading towards minimal catalytic systems that emulate some advanced traits of contemporary enzymes.

Short peptide-based cross-β amyloids exploit dual residues for phosphoesterase like activity

“…The versatility of the minimal self-assembled catalyst towards kinetically unfavourable chemical transformations, supports the argument of their role as primitive catalytic folds and also hints towards their involvement in biopolymer co-evolution. [43][44][45] Furthermore, within the limits of a short sequence such exibility along with the utilisation of a peptide registry can, in principle, process more challenging chemical transformations which were thus far believed to be achievable only by extant enzymes.…”

Construction of transient supramolecular polymers controlled by mass transfer in biphasic systems

“…Meanwhile, limited experimental parameters are involved in tuning the diffusion instead of the complex kinetic matching and harsh reaction selectivity requirements in homogeneous systems. This strategy can be further extended to multi-compartment systems 45,46 and liquidliquid phase separation systems. [47][48][49][50] Passive diffusion and active transport can be developed in controlling the transport of chemical fuels or deactivators between compartments.…”

Cross β Amyloid Nanotubes Demonstrate Promiscuous Catalysis in a Chemical Reaction Network via Co‐option

“…Due to the known capabilities of primary amines such as natural lysines to form imines and possibility of promoting transimination reaction to yield the condensation product, C2‐Lys nanotubes were used. It was expected that the β‐sheet‐rich nanotubular surface of the 17 LVFF 21 A amyloid core would offer a co‐linear array of lysines that could be conducive to the imine bond formation [20, 26, 29] . The condensation reaction leading to the formation of hydrazone was probed.…”

“…[11,12] The earliest rudimentary protein folds have been argued to be short peptides that can assemble in harsh conditions to access remarkably ordered para-crystalline folded structures. [13][14][15][16][17][18][19][20][21][22][23] Herein, we report the cross β assemblies of a short peptide that can demonstrate catalytic promiscuity to facilitate three metabolically relevant orthogonal chemical transformations (CÀ C and CÀ O bond cleavage and C=N bond condensation) and importantly, create a network that benefits the connected transformations. The benefits originate from the gradual pH modulation (hydrolase-like activity) to substrate regeneration (aldolase-like activity) to facilitate the condensation reaction in water.…”

“…It was expected that the β-sheet-rich nanotubular surface of the 17 LVFF 21 A amyloid core would offer a co-linear array of lysines that could be conducive to the imine bond formation. [20,26,29] The condensation reaction leading to the formation of hydrazone was probed. The rate of formation of hydrazone (3) in presence of C2-Lys ([v i ] C2-Lys = (6.7 � 0.5) × 10 À 2 μM min À 1 ) was found to be significantly higher than the background (Figure 2F, Table S1).…”