Evidence map›Paper›PMID 33383257›Full record

ArticleEuropean journal of medicinal chemistry2021

Stereoselective synthesis of novel 2'-(S)-CCG-IV analogues as potent NMDA receptor agonists.

Alex Maolanon, Athanasios Papangelis, David Kawiecki, Tung-Chung Mou, Jed T Syrenne, Feng Yi, Kasper B Hansen, Rasmus P Clausen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Alex MaolanonDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK, 2100, Copenhagen, Denmark.
Athanasios PapangelisDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK, 2100, Copenhagen, Denmark.
David KawieckiDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK, 2100, Copenhagen, Denmark.
Tung-Chung MouDivision of Biological Sciences, University of Montana, Missoula, MT, 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT, 59812, USA.
Jed T SyrenneDivision of Biological Sciences, University of Montana, Missoula, MT, 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT, 59812, USA; Center for Structural and Functional Neuroscience, University of Montana, Missoula, MT, 59812, USA.
Feng YiDivision of Biological Sciences, University of Montana, Missoula, MT, 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT, 59812, USA; Center for Structural and Functional Neuroscience, University of Montana, Missoula, MT, 59812, USA.
Kasper B HansenDivision of Biological Sciences, University of Montana, Missoula, MT, 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT, 59812, USA; Center for Structural and Functional Neuroscience, University of Montana, Missoula, MT, 59812, USA.
Rasmus P ClausenDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK, 2100, Copenhagen, Denmark. Electronic address: rac@sund.ku.dk.

Funding

Surveillance genome sequencing to detect SARS-CoV-2 virus variants in MontanaP20GM103546 · NIGMS · UNIVERSITY OF MONTANA · PI BOWLER, BRUCE E · 2012 to 2021
$19.2M
Structural and functional investigation of negative allosteric NMDA receptor modulationR01NS097536 · NINDS · UNIVERSITY OF MONTANA · PI Kasper Boe Hansen · 2016 to 2026
$3.4M
NIGMS NIH HHS P20 GM103546NINDS NIH HHS R01 NS097536
6 · The paper itself

Abstract

We developed a versatile stereoselective route for the synthesis of new 2'-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2'-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D receptors, demonstrating that agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2'-butyl-(S)-CCG-IV that determines the position of 2'-substituents in (S)-CCG-IV agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA receptor agonists and other applications.

Indexed as

Amino Acids, DicarboxylicCrystallography, X-RayDose-Response Relationship, DrugHumansModels, MolecularMolecular StructureReceptors, N-Methyl-D-AspartateStereoisomerismStructure-Activity Relationship(alpha-carboxycyclopropyl)glycineAmino Acids, DicarboxylicReceptors, N-Methyl-D-Aspartate(carboxycyclopropyl)glycineNMDASynthesisX-ray crystallography

Identifiers

PMID33383257
PMCPMC8325387

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.