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Biomacromolecules
02 11, 2019;20 (2): 1077-1086.

Supramolecular Tuning of HS Release from Aromatic Peptide Amphiphile Gels: Effect of Core Unit Substituents.

Yun Qian, Kuljeet Kaur, Jeffrey C Foster, John B Matson
Author Information
  1. Yun Qian: Department of Chemistry, Macromolecules Innovation Institute, and Virginia Tech Center for Drug Discovery , Virginia Tech , Blacksburg , Virginia 24061 , United States.
  2. Kuljeet Kaur: Department of Chemistry, Macromolecules Innovation Institute, and Virginia Tech Center for Drug Discovery , Virginia Tech , Blacksburg , Virginia 24061 , United States.
  3. Jeffrey C Foster: Department of Chemistry, Macromolecules Innovation Institute, and Virginia Tech Center for Drug Discovery , Virginia Tech , Blacksburg , Virginia 24061 , United States.
  4. John B Matson: Department of Chemistry, Macromolecules Innovation Institute, and Virginia Tech Center for Drug Discovery , Virginia Tech , Blacksburg , Virginia 24061 , United States. ORCID
PMID: 30676716 DOI: 10.1021/acs.biomac.8b01732

Abstract

HS is a gasotransmitter with several physiological roles, but its reactivity and short half-life in biological media make its controlled delivery difficult. For biological applications of the gas, hydrogels have the potential to deliver HS with several advantages over other donor systems, including localized delivery, controlled release rates, biodegradation, and variable mechanical properties. In this study, we designed and evaluated peptide-based HS-releasing hydrogels with controllable HS delivery. The hydrogels were prepared from short, self-assembling aromatic peptide amphiphiles (APAs), functionalized on their N-terminus with S-aroylthiooximes (SATOs), which release HS in response to a thiol trigger. The APAs were studied both in solution and in gel forms, with gelation initiated by addition of CaCl. Various substituents were included on the SATO component of the APAs in order to evaluate their effects on self-assembled morphology and HS release rate in both the solution and gel phases. Transmission electron microscopy (TEM) images confirmed that all HS-releasing APAs self-assembled into nanofibers above a critical aggregation concentration (CAC) of ∼0.5 mg/mL. Below the CAC, substituents on the SATO group affected HS release rates predictably in line with electronic effects (Hammett σ values) according to a linear free energy relationship. Above the CAC, circular dichroism, infrared, and fluorescence spectroscopies demonstrated that substituents influenced the self-assembled structures by affecting hydrogen bonding (β-sheet formation) and π-π stacking. At these concentrations, electronic control over release rates diminished, both in solution and in the gel form. Rather, the release rate depended primarily on the degree of organization in the β-sheets and the amount of π-π stacking. This supramolecular control over release rate may enable the evaluation of HS-releasing hydrogels with different release rates in biological applications.

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Grants

  1. R01 GM123508/NIGMS NIH HHS

MeSH Term

Circular Dichroism
Hydrogels
Hydrogen Bonding
Hydrogen Sulfide
Microscopy, Electron, Transmission
Nanofibers
Peptides
Spectrometry, Fluorescence
Spectrophotometry, Infrared

Chemicals

Hydrogels
Peptides
Hydrogen Sulfide
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.
Article has an altmetric score of 6

Word Cloud

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