Platinum(iv) oxaliplatin-peptide conjugates targeting memHsp70+ phenotype in colorectal cancer cells

Chem Commun (Camb). 2017 Oct 12;53(82):11318-11321. doi: 10.1039/c7cc04764a.

Abstract

Novel Pt(iv) tumour penetrating peptide (TPP) conjugates are reported. They are the first example of metallodrugs to target a membrane bound heat shock protein 70 positive (memHSP70+) phenotype in cancer cells. The conjugates exhibit superior cytotoxicity as compared to oxaliplatin alone in Pt resistant colorectal cancer cells with relatively high memHSP70+ expression. Substitution of TPP in Pt(iv) peptide conjugates with scrambled peptide (ScP) essentially abolishes the observed cytotoxicity.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • HCT116 Cells
  • HSP70 Heat-Shock Proteins / metabolism*
  • HT29 Cells
  • Humans
  • Organoplatinum Compounds / chemistry*
  • Oxaliplatin
  • Peptides / chemistry*
  • Platinum / chemistry*

Substances

  • Antineoplastic Agents
  • HSP70 Heat-Shock Proteins
  • Organoplatinum Compounds
  • Peptides
  • Oxaliplatin
  • Platinum