Evolving nanomaterials using enzyme-driven dynamic peptide libraries (eDPL)

Das, Apurba K. and Hirst, Andrew R. and Ulijn, Rein V. (2009) Evolving nanomaterials using enzyme-driven dynamic peptide libraries (eDPL). Faraday Discussions, 143. pp. 293-303. ISSN 1359-6640 (http://dx.doi.org/10.1039/b902065a)

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Abstract

This paper describes the application of dynamic combinatorial libraries (DCL) towards the discovery of self-assembling nanostructures based on aromatic peptide derivatives and the continuous enzymatic exchange of amino acid sequences. Ultimately, the most thermodynamically stable self-assembling structures will dominate the system. In this respect, a library of precursor components, based on N-fluorenyl-9-methoxycarbonyl (Fmoc)-amino acids (serine, S and threonine, T) and nucleophiles (leucine, L-; phenylalanine, F-; tyrosine, Y-; valine, V-; glycine, G-; alanine, A-OMe amino-acid esters) were investigated to produce Fmoc-dipeptide esters, denoted Fmoc-XY-OMe. Upon exposure to a protease (thermolysin), which catalyses peptide bond formation and hydrolysis under aqueous conditions at pH 8, dynamic libraries of self-assembling gelator species were generated. Depending on the molecular composition of the precursors present in the library different behaviours were observed. Single components, Fmoc-SF-OMe and Fmoc-TF-OMe, dominated over time in Fmoc-S/(L+F+Y+V+G+A)-OMe and Fmoc-T/(L+F+Y+V+G+A)-OMe libraries. This represented >80% of all peptide formed suggesting that a single component molecular structure dominates in these systems. In a competition experiment between Fmoc-(S+T)/F-OMe, conversions to each peptide corresponded directly with ratios of starting materials, implying that a bi-component nanostructure, where Fmoc-TF-OMe and Fmoc-SF-OMe are incorporated equally favourably, was formed. Several techniques including HPLC, LCMS and fluorescence spectroscopy were used to characterize library composition and molecular interactions within the self-selecting libraries. Fluorescence spectroscopy analysis suggests that the most stable peptide nanostructures show significant - intermolecular electronic communication. Overall, the paper demonstrates a novel evolution-based approach with self-selection and amplification of supramolecular peptide nanostructures from a complex mixture of amino acid precursors.

ORCID iDs

Das, Apurba K., Hirst, Andrew R. and Ulijn, Rein V. ORCID logoORCID: https://orcid.org/0000-0001-7974-3779;
CORE (COnnecting REpositories)