Enzymatic Control of the Conformational Landscape of Self‐Assembling Peptides

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  • Junfeng Shi
    Chemical Biological Laboratory National Cancer Institute, National Institutes of Health 376 Boyles Street Frederick MD 21702 USA
  • Galit Fichman
    Chemical Biological Laboratory National Cancer Institute, National Institutes of Health 376 Boyles Street Frederick MD 21702 USA
  • Joel P. Schneider
    Chemical Biological Laboratory National Cancer Institute, National Institutes of Health 376 Boyles Street Frederick MD 21702 USA

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<jats:title>Abstract</jats:title><jats:p>Post‐translational modification is a common mechanism to affect conformational change in proteins, which in turn, regulates function. Herein, this principle is expanded to instruct the formation of supramolecular assemblies by controlling the conformational bias of self‐assembling peptides. Biophysical and mechanical studies show that an engineered phosphorylation/dephosphorylation couple can affectively modulate the folding of amphiphilic peptides into a conformation necessary for the formation of well‐defined fibrillar networks. Negative design principles based on the incompatibility of hosting residue side‐chain point charge within hydrophobic environments proved key to inhibiting the peptide's ability to adopt its low energy fold in the assembled state. Dephosphorylation relieves this restriction, lowers the energy barrier between unfolded and folded peptide, and allows the formation of self‐assembled fibrils that contain the folded conformer, thus ultimately enabling the formation of a cytocompatible hydrogel material.</jats:p>

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