Structural Analysis, Molecular Modelling and Preliminary Competition Binding Studies of AM-DAN as a NMDA Receptor PCP-Site Fluorescent Ligand

Molecules. 2019 Nov 13;24(22):4092. doi: 10.3390/molecules24224092.


Excitotoxicity related to the dysfunction of the N-methyl-d-aspartate receptor (NMDAR) has been indicated to play an integral role in the pathophysiology of multiple disease states, including neurodegenerative disorders such as Parkinson's disease. There is a notable gap in the market for novel NMDAR antagonists, however current methods to analyse potential antagonists rely on indirect measurements of calcium flux and hazardous radioligand binding assays. Recently, a fluorescent NMDAR ligand, N-adamantan-1-yl-dimethylamino-1-naphthalenesulfonic acid, known as AM-DAN was developed by our group. Additional studies on this ligand is necessary to evaluate its potential as a biological tool in NMDAR research. Therefore, this study was aimed at conducting structural analyses, fluorescence experiments, high-accuracy NMDAR molecular modelling and NMDAR phencyclidine (PCP) site competition binding studies using AM-DAN. Results revealed that AM-DAN has appropriate structural properties, significant fluorescent ability in various solvents and is able to bind selectively and compete for the PCP-binding site of the NMDAR. Therefore, AM-DAN holds promise as a novel fluorescent ligand to measure the affinity of prospective drugs binding at the NMDAR PCP-site and may circumvent the use of radioligands.

Keywords: NMDAR; amantadine; dansyl; energy minima; fluorescent bioassay; fluorescent ligand; molecular modelling.

MeSH terms

  • Binding Sites*
  • Binding, Competitive*
  • Drug Discovery*
  • Fluorescent Dyes
  • Ligands*
  • Models, Molecular*
  • Molecular Conformation
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Structure-Activity Relationship


  • Fluorescent Dyes
  • Ligands
  • Receptors, N-Methyl-D-Aspartate