Lipidation at the C- or N-terminus is a powerful tool to additionally enhance the stability of peptide structures and to tune peptide self-assembly propensity. Peptide coiled-coil aggregate (12−19) and nanofibril (20−23) and nanotube (24−29) structures also have great potential in this respect due to the high degree of internal order, the potential stability of β-sheet and α-helical structures to temperature and pH changes, and the anisotropic presentation of functional (catalytic) residues at high density. A variety of self-assembled peptide nanostructures have been used to enhance catalytic activity, including micelles and vesicles in which the peptide often lacks a highly ordered conformation. Peptides have advantages as biocatalysts since they are bioderived molecules which can be obtained and purified easily and they enable the design of functional biomolecules using recently established design principles including the control of nanostructure (tertiary structure in the nomenclature of proteins). Self-assembled peptide nanostructures can be used to position catalytic residues and/or cofactors in defined positions to enhance catalytic performance under mild aqueous conditions and to permit operation under nonambient conditions. (4−11) The present Review is focused on the use of self-assembled peptide structures in biocatalysis. This behavior has been reviewed in detail elsewhere. Several classes of peptides including surfactant-like peptides, amyloid peptides, and lipopeptides (a type of peptide amphiphile) can aggregate in aqueous solution into a range of nanostructures depending on intermolecular forces, especially hydrophobic interactions which are balanced by hydrogen-bonding, electrostatic, and π-stacking interactions leading to different self-assembled morphologies. Advances in peptide design and synthesis methods mean they hold great potential for future developments of effective bioinspired and biocompatible catalysts.
Research showing the high activities of different classes of peptides in catalyzing many reactions is highlighted. Research on these topics is summarized, along with a discussion of metal nanoparticle catalysts templated by peptide nanostructures, especially fibrils. 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. 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. 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. 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.