The living world provides ample evidence demonstrating that peptides are powerful building blocks for the formation of supramolecular materials, selective binders and catalysts. However, biological systems are complex and fragile limiting their technological applications. We are developing methodology which allows function to be identified in minimalistic, <i>de novo</i> sequences that are not inspired or informed by biological macromolecules but identified by unbiased searching for function in the peptide sequence space. The design and selection of functional peptide sequences is, however, challenging because of the vast combinatorial space available. In this talk we will report our latest data on the use of computational and experimental methodologies to search the peptide sequence space for function. In particular, dynamic peptide libraries (DPL) will be discussed as a tool enabling the peptide sequence space to be searched for self-assembling and templating structures. In this approach, unprotected homo- and hetero-dipeptides (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 (or co-assembly, or binding) 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.

Exploring the peptide sequence space for function

253rd National Meeting (2017)

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