Amine-bearing hydrocarbon cross-links: Tailoring helix stability, hydrophilicity, and synthetic adaptability in peptides

Bioorg Med Chem. 2024 Oct 1:112:117893. doi: 10.1016/j.bmc.2024.117893. Epub 2024 Aug 22.

Abstract

This study comprehensively explored the helix-stabilizing effects of amine-bearing hydrocarbon cross-links (ABXs), revealing their context-dependent nature influenced by various structural parameters. Notably, we identified a 9-atom ABX as a robust helix stabilizer, showcasing versatile synthetic adaptability while preserving peptide water solubility. Future investigations are imperative to fully exploit this system's potential and enrich our chemical toolkit for designing innovative peptide-based biomolecules.

Keywords: Amine cross-link; Peptide drugs; Peptide stapling; Ring-closing metathesis; α-Helix.

MeSH terms

  • Amines* / chemical synthesis
  • Amines* / chemistry
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / chemistry
  • Hydrocarbons* / chemical synthesis
  • Hydrocarbons* / chemistry
  • Hydrophobic and Hydrophilic Interactions*
  • Molecular Structure
  • Peptides* / chemical synthesis
  • Peptides* / chemistry
  • Solubility

Substances

  • Peptides
  • Amines
  • Hydrocarbons
  • Cross-Linking Reagents