Emergent Catalytic Behavior of Self‐Assembled Low Molecular Weight Peptide‐Based Aggregates and Hydrogels

Abstract

We report a series of short peptides possessing the sequence (FE)n or (EF)n and bearing l-proline at their N-terminus that self-assemble into high aspect ratio aggregates and hydrogels. We show that these aggregates are able to catalyze the aldol reaction, whereas non-aggregated analogues are catalytically inactive. We have undertaken an analysis of the results, considering the accessibility of catalytic sites, pKa value shifts, and the presence of hydrophobic pockets. We conclude that the presence of hydrophobic regions is indeed relevant for substrate solubilization, but that the active site accessibility is the key factor for the observed differences in reaction rates. The results presented here provide an example of the emergence of a new chemical property caused by self-assembly, and support the relevant role played by self-assembled peptides in prebiotic scenarios. In this sense, the reported systems can be seen as primitive aldolase I mimics, and have been successfully tested for the synthesis of simple carbohydrate precursors.

Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self‐Assembling Peptide

“…The use of peptides has the advantage that the known catalytic activities of amino acid residues in natural enzymes can be incorporated into the artificial construct. Indeed, functioning artificial biocatalysts from self‐assembled peptides have been developed using a range of designs, including α‐helical coiled‐coils, peptide amphiphiles, short β‐sheet forming peptides,,, aromatic peptide amphiphiles, tripeptide assemblies, and bola‐type amphiphiles . These systems typically incorporate one (or more) histidine and/or other residues relevant to catalysis or binding, sometimes including metal ions to assist folding and catalysis.…”

Prebiotic synthesis of 2-deoxy-d-ribose from interstellar building blocks promoted by amino esters or amino nitriles

“…18,24,25 Initial studies with amino acid promoted aldol reactions focused on the formation of tetroses. 18,26 Pizzarello and Weber showed the dimerization of glycolaldehyde by a,a-L-disubstituted amino acids led to the formation of L-tetroses in o7% ee. 18 Similar studies by…”

Visible-light photooxidation in water by 1O2-generating supramolecular hydrogels

“…[15][16][17][18][19] Hydrogel networks can address the solubility problem because hydrophobic aromatic compounds oen associate into the nanober network in water and become reactively accessible. 20 For example, the Meijer 21 and Escuder 22 groups have shown that a self-assembled, 1D ber network enhances catalytic activity compared to its non-assembled counterpart. [23][24][25][26][27][28] Most recent examples of hydrogel photocatalysts 29 involve co-assembling of the photocatalysts with gelators, where catalysts and gelators are two separate components.…”