Synthesis and activity of tumor-homing peptide iRGD and histone deacetylase inhibitor valproic acid conjugate

Bioorg Med Chem Lett. 2014 Apr 15;24(8):1928-33. doi: 10.1016/j.bmcl.2014.03.006. Epub 2014 Mar 12.

Abstract

In this Letter, we present a concise strategy to prepare a conjugate of the tumor homing peptide iRGD and histone deacetylase inhibitor valproic acid, VPA-GFLG-iRGD. The conjugate VPA-GFLG-iRGD and a mixture of VPA and GFLG-iRGD have shown similar cytotoxicity against DU-145 prostate cancer cells. However, the treatment of DU-145 cells with conjugate VPA-GFLG-iRGD resulted in a decreased percentage of cells in the G2 phase, whereas the exposure of a mixture of VPA and GFLG-iRGD led to an increased percentage of cells in the G2 phase. We also found that GFLG-iRGD possessed cytotoxicity at the tested concentrations.

Keywords: Cell cycle arrest; Cell penetrating peptide; Histone deacetylase inhibitor; Valproic acid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Male
  • Molecular Structure
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Valproic Acid / chemical synthesis
  • Valproic Acid / chemistry*
  • Valproic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Oligopeptides
  • Valproic Acid
  • arginyl-glycyl-aspartic acid