Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 6 November 2019 / Approved: 7 November 2019 / Online: 7 November 2019 (04:17:07 CET)

A peer-reviewed article of this Preprint also exists.

Ndzibongwana, S.; Ngobese, S.; Sayed, A.; Shongwe, C.; White-Phillips, S.; Joubert, J. Structural Analysis, Molecular Modelling and Preliminary Competition Binding Studies of AM-DAN as a NMDA Receptor PCP-Site Fluorescent Ligand. Molecules 2019, 24, 4092. Ndzibongwana, S.; Ngobese, S.; Sayed, A.; Shongwe, C.; White-Phillips, S.; Joubert, J. Structural Analysis, Molecular Modelling and Preliminary Competition Binding Studies of AM-DAN as a NMDA Receptor PCP-Site Fluorescent Ligand. Molecules 2019, 24, 4092.

Journal reference: Molecules 2019, 24, 4092
DOI: 10.3390/molecules24224092

Abstract

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 analyze 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.

Subject Areas

NMDAR; amantadine; dansyl; fluorescent ligand; energy minima; molecular modelling; fluorescent bioassay

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