Caspase-3 mediated programmed cell death by a gold-stabilised peptide carbene

Bioorg Med Chem Lett. 2019 Nov 1;29(21):126672. doi: 10.1016/j.bmcl.2019.126672. Epub 2019 Sep 12.

Abstract

The synthesis of novel N-heterocyclic carbene complexes derived from a tripeptide ligand (L), containing non-natural amino acid, thiazolylalanine is described here. The peptide ligand was reacted with suitable precursors to generate gold and mercury carbene complexes. The plausible structures of both complexes were predicted by spectroscopic data and DFT calculations. The binding energy data was also analyzed to predict their stability. The gold carbene complex (1A), showed activity against MCF7 breast cancer cell line due to mitochondrial triggered caspase-3 mediated programmed cell death. Its internalization inside cells could be observed due to autofluorescence. This study affords a methodology for successful generation of peptide carbene complexes for their therapeutic potential.

Keywords: Caspase-3; Gold carbene; Peptide; Programmed cell death; Thiazolylalanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Amino Acids / chemistry
  • Apoptosis / drug effects*
  • Caspase 3 / chemistry*
  • Caspase 3 / metabolism
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / metabolism
  • Density Functional Theory
  • Fluorescent Dyes / chemistry
  • Gold / chemistry*
  • Humans
  • Ligands
  • MCF-7 Cells
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Methane / metabolism
  • Models, Molecular
  • Molecular Structure
  • Optical Imaging
  • Peptides / chemistry*
  • Peptides / metabolism

Substances

  • Amino Acids
  • Coordination Complexes
  • Fluorescent Dyes
  • Ligands
  • Peptides
  • carbene
  • Gold
  • CASP3 protein, human
  • Caspase 3
  • Methane