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.
Astha Gupta  1 ,  Shivansh Nigam  2 ,  Ilesha Avasthi  3 ,  Bikramjit Sharma  3 ,  Bushra Ateeq  2 ,  Sandeep Verma  4
Affiliations
  • 1. Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, India.
  • 2. Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, India.
  • 3. Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, India.
  • 4. Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, India. Electronic address: [email protected].
PMID: 31570209 DOI: 10.1016/j.bmcl.2019.126672
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.
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