Structural Consequences of Introducing Bioactive Domains to Designer β-Sheet Peptide Self-Assemblies

Alicia S. Robang, Abhishek Roy, Joseph B. Dodd-O, Dongjing He, Justin V. Le, Andrew C. McShan, Yuhang Hu, Vivek A. Kumar, Anant K. Paravastu

Research output: Contribution to journalArticlepeer-review

Abstract

We applied solid- and solution-state nuclear magnetic resonance spectroscopy to examine the structure of multidomain peptides composed of self-assembling β-sheet domains linked to bioactive domains. Bioactive domains can be selected to stimulate specific biological responses (e.g., via receptor binding), while the β-sheets provide the desirable nanoscale properties. Although previous work has established the efficacy of multidomain peptides, molecular-level characterization is lacking. The bioactive domains are intended to remain solvent-accessible without being incorporated into the β-sheet structure. We tested for three possible anticipated molecular-level consequences of introducing bioactive domains to β-sheet-forming peptides: (1) the bioactive domain has no effect on the self-assembling peptide structure; (2) the bioactive domain is incorporated into the β-sheet nanofiber; and (3) the bioactive domain interferes with self-assembly such that nanofibers are not formed. The peptides involved in this study incorporated self-assembling domains based on the (SL)6 motif and bioactive domains including a VEGF-A mimic (QK), an IGF-mimic (IGF-1c), and a de novo SARS-CoV-2 binding peptide (SBP3). We observed all three of the anticipated outcomes from our examination of peptides, illustrating the unintended structural effects that could adversely affect the desired biofunctionality and biomaterial properties of the resulting peptide hydrogel. This work is the first attempt to evaluate the structural effects of incorporating bioactive domains into a set of peptides unified by a similar self-assembling peptide domain. These structural insights reveal unmet challenges in the design of highly tunable bioactive self-assembling peptide hydrogels.

Original languageEnglish (US)
Pages (from-to)1429-1438
Number of pages10
JournalBiomacromolecules
Volume25
Issue number3
DOIs
StatePublished - Mar 11 2024

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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