Sequence-specific polymers, such as oligonucleotides and peptides, can be used as building blocks for functional supramolecular nanomaterials. The design and selection of suitable self-assembling sequences is, however, challenging because of the vast combinatorial space available. Here we report a methodology that allows the peptide sequence space to be searched for self-assembling structures. In this approach, unprotected homo- and heterodipeptides (including aromatic, aliphatic, polar and charged amino acids) are subjected to continuous enzymatic condensation, hydrolysis and sequence exchange to create a dynamic combinatorial peptide library. The free-energy change associated with the assembly process itself gives rise to selective amplification of self-assembling candidates. By changing the environmental conditions during the selection process, different sequences and consequent nanoscale morphologies are selected.

Aqueous compatible supramolecular materials hold promise for applications in environmental remediation, energy harvesting and biomedicine. One remaining challenge is to actively select a target structure from a multitude of possible options, in response to chemical signals, while maintaining constant, physiological conditions. Here, we demonstrate the use of amino acids to actively decorate a self-assembling core molecule in situ, thereby controlling its amphiphilicity and consequent mode of assembly. The core molecule is the organic semiconductor naphthalene diimide, functionalized with D- and L- tyrosine methyl esters as competing reactive sites. In the presence of α-chymotrypsin and a selected encoding amino acid, kinetic competition between ester hydrolysis and amidation results in covalent or non-covalent amino acid incorporation, and variable supramolecular self-assembly pathways. Taking advantage of the semiconducting nature of the naphthalene diimide core, electronic wires could be formed and subsequently degraded, giving rise to temporally regulated electro-conductivity.

The controlled self‐assembly of porphyrin derivatives (TCPP, tetrakis(4‐carboxyphenyl)porphyrin) within Fmoc‐protected (Fmoc=9‐Fluorenylmethyloxycarbonyl) dipeptide (Fmoc‐TL‐NH2) nanofibers is demonstrated. The biocatalytic co‐assembly in aqueous medium generated an energy transfer hydrogel. Depending on the concentrations of porphyrin used, the resulting nanofibrous gels show two distinct regions of self‐assembly behavior that is, integration of TCPP into nanostructures to produce two‐component co‐assembly fibers, or heterogeneous self‐aggregation of TCPP within the self‐assembled matrix observed at higher concentrations. The mode of assembly directly impacts on the energy transfer efficiency of these nanostructures. These results show that reversible biocatalytic co‐assembly of structural and functional components enables fine‐tuning of peptide/porphyrin energy transfer nanostructures.