Tunable Supramolecular Assemblies from Amphiphilic Nucleoside Phosphoramidate Nanofibers by Enzyme Activation

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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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
Issue number7
StatePublished - Jul 9 2018

Bibliographical note

Funding Information:
Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. We gratefully acknowledge Dr. Bob Hafner (Characterization Facility, University of Minnesota) for his assistance with the transmission electron microscopy experiments. Oscillatory rheometry was performed in the University of Minnesota Polymer Characterization Facility. We gratefully acknowledge David Giles for assistance with these experiments. This work was supported by the National Institutes of Health R21 CA185627 (C.R.W.), F30 CA210345 (C.M.C.), NIH T32 GM008244 (C.M.C.), and the University of Minnesota.

Publisher Copyright:
Copyright © 2018 American Chemical Society.


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