Synthesis and Cytotoxicity of Cyclic Octapeptide Surugamides with Varied N-Acyl Moieties

Chem Pharm Bull (Tokyo). 2024;72(9):826-830. doi: 10.1248/cpb.c24-00533.

Abstract

Surugamides are a group of non-ribosomal peptides produced by Streptomyces spp. Several derivatives possess acyl groups, which are proposed to be attached to a lysine side chain after backbone-macrocyclization during biosynthesis. To date, five different acyl groups have been identified in nature, yet their impacts on biological activity remain underexplored. Here we synthesized surugamide B derivatives with varied acyl moieties. Biological evaluations revealed that larger hydrophobic acyl groups on lysine ε-NH2 enhance cytotoxicity.

Keywords: acylation; cyclic peptide; non-ribosomal peptide.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Peptides, Cyclic* / chemical synthesis
  • Peptides, Cyclic* / chemistry
  • Peptides, Cyclic* / pharmacology
  • Streptomyces / chemistry
  • Structure-Activity Relationship

Substances

  • Peptides, Cyclic
  • Antineoplastic Agents