Self-assembly of bio-inspired heterochiral peptides

Bioorg Chem. 2021 Sep:114:105047. doi: 10.1016/j.bioorg.2021.105047. Epub 2021 May 30.

Abstract

Peptide hydrogels, deriving from natural protein fragments, present unique advantages as compatibility and low cost of production that allow their wide application in different fields as wound healing, cell delivery and tissue regeneration. To engineer new biomaterials, the change of the chirality of single amino acids demonstrated a powerful approach to modulate the self-assembly mechanism. Recently we unveiled that a small stretch spanning residues 268-273 in the C-terminal domain (CTD) of Nucleophosmin 1 (NPM1) is an amyloid sequence. Herein, we performed a systematic D-scan of this sequence and analyzed the structural properties of obtained peptides. The conformational and kinetic features of self-aggregates and the morphologies of derived microstructures were investigated by means of different biophysical techniques, as well as the compatibility of hydrogels was evaluated in HeLa cells. All the investigated hexapeptides formed hydrogels even if they exhibited different conformational intermediates during aggregation, and they structural featured are finely tuned by introduced chiralities.

Keywords: Compatibilty; Heterochirality; Peptide hydrogels; SEM.

MeSH terms

  • Cell Proliferation / drug effects
  • HeLa Cells
  • Humans
  • Hydrogels / chemistry*
  • Hydrogels / toxicity
  • Nucleophosmin / chemistry*
  • Nucleophosmin / toxicity
  • Oligopeptides / chemistry*
  • Oligopeptides / toxicity
  • Peptide Fragments / chemistry*
  • Peptide Fragments / toxicity
  • Protein Multimerization
  • Stereoisomerism

Substances

  • Hydrogels
  • Oligopeptides
  • Peptide Fragments
  • Nucleophosmin