Inducible expression and pharmacology of recombinant NMDA receptors, composed of rat NR1a/NR2B subunits

Nagy, J; Boros, András; Dezső, Péter; Kolok, Sándor; Fodor, László

doi:10.1016/s0197-0186(02)00198-5

Cited by 21 publications

(8 citation statements)

References 38 publications

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“…3). Some of the most effective substitutions of the B ring among ifenprodil analogs have been 5-hydroxy-benzimidazole, para-N-phenylmethanesulfonamide, benzoxazolinone, and benzimidazolinone (Wright et al, 2000;Nagy et al, 2003;Barta-Szalai et al, 2004;McCauley et al, 2004;Tahirovic et al, 2008;Mony et al, 2009a;Mosley et al, 2009). Docking compounds with different B-ring moieties showed that the hydroxyl-containing groups exhibited a pose similar to ifenprodil and Ro 25-6981, forming hydrogen bonds with Glu236 and a water molecule (Figs.…”

Section: Glun2b-selective Allosteric Modulator Binding 349mentioning

confidence: 99%

Mapping the Binding of GluN2B-SelectiveN-Methyl-d-aspartate Receptor Negative Allosteric Modulators

Burger¹,

Yuan²,

Karakaş³

et al. 2012

Mol Pharmacol

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We have used recent structural advances in our understanding of the N-methyl-D-aspartate (NMDA) receptor amino terminal domain to explore the binding mode of multiple diaryl GluN2B-selective negative allosteric modulators at the interface between the GluN1 and GluN2B amino-terminal domains. We found that interaction of the A ring within the binding pocket seems largely invariant for a variety of structurally distinct ligands. In addition, a range of structurally diverse linkers between the two aryl rings can be accommodated by the binding site, providing a potential opportunity to tune interactions with the ligand binding pocket via changes in hydrogen bond donors, acceptors, as well as stereochemistry. The most diversity in atomic interactions between protein and ligand occur in the B ring, with functional groups that contain electron donors and acceptors providing additional atomic contacts within the pocket. A cluster of residues distant to the binding site also control ligand potency, the degree of inhibition, and show ligand-induced increases in motion during molecular dynamics simulations. Mutations at some of these residues seem to distinguish between structurally distinct ligands and raise the possibility that GluN2B-selective ligands can be divided into multiple classes. These results should help facilitate the development of well tolerated GluN2B subunit-selective antagonists.

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Section: Glun2b-selective Allosteric Modulator Binding 349mentioning

confidence: 99%

Mapping the Binding of GluN2B-SelectiveN-Methyl-d-aspartate Receptor Negative Allosteric Modulators

Burger¹,

Yuan²,

Karakaş³

et al. 2012

Mol Pharmacol

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“…Biological activity of the prepared compounds was measured in a binding assay using tritiated Ro-25,6981 as radioligand 7;18;19 and in a functional assay where the inhibition of NMDA-evoked increase of intracellular Ca 2þ level was determined on cells expressing recombinant NR1/NR2B receptors 20 (Table 1). Baseline and NMDA-evoked changes of intracellular Ca 2þ were monitored by fluorimetry using a Ca 2þ -selective fluorescent dye (Fluo-4/AM) and a plate reader fluorimeter.…”

Section: Ci-1041mentioning

confidence: 99%

“…Baseline and NMDA-evoked changes of intracellular Ca 2þ were monitored by fluorimetry using a Ca 2þ -selective fluorescent dye (Fluo-4/AM) and a plate reader fluorimeter. 20 Selectivity towards NR2A subunit-containing NMDA receptors was tested by the same functional assay using cells expressing recombinant NR1/NR2A receptors and none of the compounds exhibited significant activity up to 15 lM concentration. In vivo analgesic activity was tested in the mouse formalin test 21;22 a model of persistent pain.…”

Section: Ci-1041mentioning

confidence: 99%

Oxamides as novel NR2B selective NMDA receptor antagonists

Barta‐Szalai

Borza

Bozó

et al. 2004

Bioorganic & Medicinal Chemistry Letters

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“…To date, the regulated expression of a range of genes has been reported, including numerous extracellular receptors, transporters, and adhesion molecules (8)(9)(10)(11)(12)(13)(14)(15), apoptosis inhibitors and inducers (16,17), genes involved in development, signal transduction, and growth regulation pathways (18)(19)(20), and potentially therapeutic genes (21). The system has been used for conditional knockouts by controlled expression of dominant negative genes and antisense RNA (20) and by conditional expression of a site-specific recombinase for gene targeting (22), and its successful use has been reported in diverse cell types, including cancer cell lines (19,23) and neuronal (15,24), skeletal muscle (20,25), and mammary cells.…”

Section: Introductionmentioning

confidence: 99%

Retroviral Delivery of the Ecdysone‐Regulatable Gene Expression System

Vaillancourt¹,

Felts²

2003

Biotechnology Progress

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We describe a set of Moloney Murine Leukemia Virus (MoMLV)-based replication-defective retroviral vectors for delivery of the ecdysone-inducible system into mammalian cells. The vector pFB-ERV contains a tricistronic CMV expression cassette from which the ecdysone receptor proteins RXR and VgEcR are expressed, with the neo-resistance marker expressed as the third open reading frame (ORF). The inducible vector pCFB-EGSH contains an ecdysone-inducible expression cassette inserted between the viral LTRs in the antisense orientation relative to that for the viral promoter. Potential interference from the proviral 5' LTR is obviated due to a SIN deletion in the 3' LTR. When used together, induction ratios of over 1000-fold were achieved in NIH3T3 cells using firefly luciferase as a reporter.

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Inducible expression and pharmacology of recombinant NMDA receptors, composed of rat NR1a/NR2B subunits

Cited by 21 publications

References 38 publications

Mapping the Binding of GluN2B-SelectiveN-Methyl-d-aspartate Receptor Negative Allosteric Modulators

Mapping the Binding of GluN2B-SelectiveN-Methyl-d-aspartate Receptor Negative Allosteric Modulators

Oxamides as novel NR2B selective NMDA receptor antagonists

Retroviral Delivery of the Ecdysone‐Regulatable Gene Expression System

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