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

Apurba K. Das, Andrew R. Hirst, Rein V. Ulijn

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.
LanguageEnglish
Pages293-303
Number of pages10
JournalFaraday Discussions
Volume143
DOIs
Publication statusPublished - 1 Jul 2009

Fingerprint

Peptide Library
Nanostructured materials
peptides
enzymes
Peptides
Nanostructures
Enzymes
amino acids
assembling
Amino Acids
Fluorescence spectroscopy
Esters
esters
Thermolysin
Nucleophiles
Molecular interactions
Dipeptides
Valine
fluorescence
leucine

Keywords

  • nanomaterials
  • enzyme-driven dynamic peptide libraries
  • eDPL
  • dynamic combinatorial libraries
  • DCL
  • nanostructures
  • amino acid sequences

Cite this

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title = "Evolving nanomaterials using enzyme-driven dynamic peptide libraries (eDPL)",
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.",
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Evolving nanomaterials using enzyme-driven dynamic peptide libraries (eDPL). / Das, Apurba K.; Hirst, Andrew R.; Ulijn, Rein V.

In: Faraday Discussions, Vol. 143, 01.07.2009, p. 293-303.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Das, Apurba K.

AU - Hirst, Andrew R.

AU - Ulijn, Rein V.

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N2 - 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.

AB - 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.

KW - nanomaterials

KW - enzyme-driven dynamic peptide libraries

KW - eDPL

KW - dynamic combinatorial libraries

KW - DCL

KW - nanostructures

KW - amino acid sequences

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