Tunable Supramolecular Assemblies from Amphiphilic Nucleoside Phosphoramidate Nanofibers by Enzyme Activation

Harrison T West, Clifford M. Csizmar, Carston R Wagner

Research output: Contribution to journalArticle

Abstract

Enzymes possess unique qualities that make them ideal regulators of supramolecular assembly. They are uniquely sensitive to biomolecules and biological compartments, catalytic in effecting chemical reactions, and present a biocompatible and degradable platform for assembly regulation. We demonstrate the novel utility of Histidine Triad Nucleotide Binding Protein 1 (HINT1) in regulating supramolecular hydrogel formation. We synthesized nucleoside-phosphoramidate-functionalized self-assembling peptides that we observed to form nanofibers. We found HINT1's catalytic hydrolysis of the nucleoside phosphoramidate moieties within the nanofiber structures to induce nanofiber organization and higher ordered assembly. The role of HINT1 in effecting this structural change was confirmed with experiments utilizing a high-affinity HINT1 inhibitor and catalytically dead HINT1 mutant. In addition, the kinetics and morphology of hydrogel formation were found to be dependent on the structure of the released nucleoside monophosphate. This work highlights the self-assembly of phosphoramidate nanofibers and their higher organization triggered by HINT1 enzymatic activity.

Original languageEnglish (US)
Pages (from-to)2650-2656
Number of pages7
JournalBiomacromolecules
Volume19
Issue number7
DOIs
StatePublished - Jul 9 2018

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Nanofibers
Nucleosides
Enzymes
Chemical activation
Hydrogel
Hydrogels
Biomolecules
Nucleotides
Histidine
Self assembly
Peptides
Chemical reactions
Hydrolysis
Carrier Proteins
Kinetics
phosphoramidic acid
Experiments

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

Cite this

Tunable Supramolecular Assemblies from Amphiphilic Nucleoside Phosphoramidate Nanofibers by Enzyme Activation. / West, Harrison T; Csizmar, Clifford M.; Wagner, Carston R.

In: Biomacromolecules, Vol. 19, No. 7, 09.07.2018, p. 2650-2656.

Research output: Contribution to journalArticle

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