Development of a carboplatin derivative conjugated with a collagen-like triple-helical peptide

Future Med Chem. 2018 Mar 1;10(6):619-629. doi: 10.4155/fmc-2017-0183. Epub 2018 Feb 7.

Abstract

Aim: The development of a platinum anticancer agent that has improved efficacy by efficient delivery to a tumor and that suppresses side effects has been investigated. Arginine-rich triple-helical peptides are promising drug carriers because of their stability in body fluids and cell-penetrating activity.

Results: We synthesized a carboplatin derivative conjugated with an arginine-rich triple-helical peptide. This derivative released platinum under acidic conditions or in the presence Cl- ions. Administration of this derivative to P388 tumor-bearing mice showed comparable survival rates to twice the dose of carboplatin, which was attributed to a longer mean residence time by pharmacokinetics analysis.

Conclusion: The collagen-like triple-helical peptide was an efficient carrier of a platinum anticancer agent because of a modification to its pharmacokinetic profile.

Keywords: antitumor agent; pharmacokinetics; triple-helical peptide.

MeSH terms

  • Animals
  • Carboplatin / chemistry*
  • Carboplatin / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell-Penetrating Peptides / chemistry*
  • Collagen / chemistry
  • Drug Design
  • Drug Stability
  • Half-Life
  • Humans
  • Male
  • Malonates / chemistry
  • Mice
  • Mice, Inbred ICR
  • Neoplasms / drug therapy
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Platinum / chemistry
  • Prodrugs / chemistry*
  • Prodrugs / pharmacokinetics
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use
  • Protein Structure, Secondary
  • Survival Rate
  • Transplantation, Heterologous

Substances

  • Cell-Penetrating Peptides
  • Malonates
  • Prodrugs
  • Platinum
  • Collagen
  • malonic acid
  • Carboplatin