Biocatalysts Based on Peptide and Peptide Conjugate Nanostructures

Abstract

Peptides and their conjugates (to lipids, bulky N-terminals, or other groups) can self-assemble into nanostructures such as fibrils, nanotubes, coiled coil bundles, and micelles, and these can be used as platforms to present functional residues in order to catalyze a diversity of reactions. Peptide structures can be used to template catalytic sites inspired by those present in natural enzymes as well as simpler constructs using individual catalytic amino acids, especially proline and histidine. The literature on the use of peptide (and peptide conjugate) α-helical and β-sheet structures as well as turn or disordered peptides in the biocatalysis of a range of organic reactions including hydrolysis and a variety of coupling reactions (e.g., aldol reactions) is reviewed. The simpler design rules for peptide structures compared to those of folded proteins permit ready ab initio design (minimalist approach) of effective catalytic structures that mimic the binding pockets of natural enzymes or which simply present catalytic motifs at high density on nanostructure scaffolds. Research on these topics is summarized, along with a discussion of metal nanoparticle catalysts templated by peptide nanostructures, especially fibrils. Research showing the high activities of different classes of peptides in catalyzing many reactions is highlighted. Advances in peptide design and synthesis methods mean they hold great potential for future developments of effective bioinspired and biocompatible catalysts.

Systems chemistry of peptide-assemblies for biochemical transformations

“…[140][141][142] It is important to note that apart from the above biochemical transformations, the peptide assemblies have been also exploited in promoting several other organocatalytic reactions such as Michael addition, Mannich reaction, etc. 143 Further, co-assembly between peptides and photosensitizers or photosensitizer-peptide conjugates has been shown to demonstrate artificial photosynthetic capabilities and various other phototherapeutic applications. [144][145][146][147]…”

Putting precision and elegance in enzyme immobilisation with bio-orthogonal chemistry

“…68 Control of macromolecular topology with genetically encoded SpyTag-SpyCatcher chemistry 69,123,131 is also used to engineer protein hydrogels from tandem modular elastomeric and enzyme proteins that can find applications in tissue engineering, controlled drug release 132 and immobilisation of enzymes in multi-enzyme nanodevices. 129,[133][134][135][136] A single target enzyme molecule can be fused to both a SpyTag and a SpyCatcher and subsequently undergo cyclisation to form circular proteins, so-called SpyRings, through intramolecular formation of the original isopeptide bond, or This journal is © The Royal Society of Chemistry 2022 formation of enzyme aggregates through intermolecular coupling. 69 Circular proteins occur widely in nature, in plants animals and bacteria, and generally exhibit exceptional thermal stability and resistance to hydrolysis and proteolysis.…”

Photo-responsive hole formation in the monolayer membrane wall of a supramolecular nanotube for quick recovery of encapsulated protein

“…Supramolecular nanotubes formed by assembly of organic molecules such as lipids possess a one-dimensional cavity with a tunable diameter and chemically functionalizable surface. 1 Because of their high aspect ratios (length/diameter > 100–100 000), these cavities can be used as containers for the slow or sustained release of drugs, channels for the transport or separation of biomolecules, and templates for the production of conformationally controlled polymers and inorganic nanorods. 2 The confinement effect of the nanotube cavity is also useful for stabilizing proteins or accelerating their refolding.…”