Cell-penetrating peptides containing 2,5-diketopiperazine (DKP) scaffolds as shuttles for anti-cancer drugs: conformational studies and biological activity

Chem Commun (Camb). 2020 May 27;56(42):5685-5688. doi: 10.1039/d0cc01490g.

Abstract

A series of linear and cyclic peptidomimetics composed of a cell-penetrating peptide and a non-natural, bifunctional 2,5-diketopiperazine scaffold is reported. Conformational studies revealed well-defined helical structures in micellar medium for linear structures, while cyclic peptidomimetics were more flexible. Biological investigations showed higher membrane-activity of cyclic derivatives allowing their use as shuttles for anti-cancer drugs.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Survival
  • Cell-Penetrating Peptides / chemical synthesis
  • Cell-Penetrating Peptides / chemistry*
  • Daunorubicin / pharmacology*
  • Diketopiperazines / chemical synthesis
  • Diketopiperazines / chemistry*
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • HeLa Cells
  • Humans
  • Micelles
  • Peptidomimetics / chemical synthesis
  • Peptidomimetics / chemistry
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Sodium Dodecyl Sulfate / chemistry
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Cell-Penetrating Peptides
  • Diketopiperazines
  • Drug Carriers
  • Micelles
  • Peptidomimetics
  • Sodium Dodecyl Sulfate
  • Daunorubicin