Catalytic diversity in self-propagating peptide assemblies

Abstract

The protein-only infectious agents known as prions exist within cellular matrices as populations of assembled polypeptide phases ranging from particles to amyloid fibres. These phases appear to undergo Darwinian-like selection and propagation, yet remarkably little is known about their accessible chemical and biological functions. Here we construct simple peptides that assemble into well-defined amyloid phases and define paracrystalline surfaces able to catalyse specific enantioselective chemical reactions. Structural adjustments of individual amino acid residues predictably control both the assembled crystalline order and their accessible catalytic repertoire. Notably, the density and proximity of the extended arrays of enantioselective catalytic sites achieve template-directed polymerization of new polymers. These diverse amyloid templates can now be extended as dynamic self-propagating templates for the construction of even more complex functional materials.

Aldolase Cascade Facilitated by Self‐Assembled Nanotubes from Short Peptide Amphiphiles

“…The above experiments suggested a positively charged surface of nanotubes with a dense array of lysines that can be exploited for catalyzing reactions by formation of imine intermediates . We investigated whether these nanotubes could catalyze retro‐aldol reactions, and importantly, whether they could show selectivity among substrates.…”

Designed Negative Feedback from Transiently Formed Catalytic Nanostructures

“…Significantly, the rates for SYS2 (average rate V i =0.6±0.01 μ m s −1 ) was an order of magnitude lower than the rapid phase of SYS1 . The lower activity in SYS2 is surprising from the context of supramolecular catalysis where pre‐assembled structures usually show augmented activity owing to the presence of a rich surface of solvent‐exposed catalytic residues . Hence, the activation in SYS1 underpinned the role of a new conformational state, augmentation of catalytic potential, and subsequent negative feedback on the stability of the nanostructures.…”

Expanding the informational chemistries of life: peptide/RNA networks

“…A simple change of the terminal amino acid from the abiotically abundant glutamic acid (E) to glutamine (Q), substituting an O atom for an NH, unmasks a kinetic selection process altering the aggregation pathway [12]. Substitution of E for the neutral leucine residue (L), Ac-KLVFFAL-NH 2 , leads to a supramolecular condensation catalyst [56]. As shown in figure 4a, this peptide assembles as structurally defined 30.8 ± 3.0 nm diameter nanotubes containing anti-parallel out-of-register strands (figure 4b).…”

“…The propensity of the amyloid assemblies to bind extended aromatic molecules suggests that they may be suitable for organizing heterocyclic RNA bases, for templated polymerization, or polycyclic aromatic hydrocarbons (PAHs), as possible precursors of early redox cofactors [56].) [60].…”