Evidence map›Paper›PMID 28407400›Full record

ArticleAngewandte Chemie (International ed. in English)2017

Designed Spiroketal Protein Modulation.

Marcel Scheepstra, Sebastian A Andrei, M Yagiz Unver, Anna K H Hirsch, Seppe Leysen, Christian Ottmann, Luc Brunsveld, Lech-Gustav Milroy

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2017. 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. Designed Spiroketal Protein Modulation.Angewandte Chemie (International ed. in English) · 2017
    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.

Marcel ScheepstraLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.
Sebastian A AndreiLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.
M Yagiz UnverStratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747AG, Groningen, The Netherlands.
Anna K H HirschStratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747AG, Groningen, The Netherlands.
Seppe LeysenLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.
Christian OttmannLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.
Luc BrunsveldLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.
Lech-Gustav MilroyLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spiroketals are structural motifs found in many biologically active natural products, which has stimulated considerable efforts toward their synthesis and interest in their use as drug lead compounds. Despite this, the use of spiroketals, and especially bisbenzanulated spiroketals, in a structure-based drug discovery setting has not been convincingly demonstrated. Herein, we report the rational design of a bisbenzannulated spiroketal that potently binds to the retinoid X receptor (RXR) thereby inducing partial co-activator recruitment. We solved the crystal structure of the spiroketal-hRXRα-TIF2 ternary complex, and identified a canonical allosteric mechanism as a possible explanation for the partial agonist behavior of our spiroketal. Our co-crystal structure, the first of a designed spiroketal-protein complex, suggests that spiroketals can be designed to selectively target other nuclear receptor subtypes.

Indexed as

Crystallography, X-RayFuransHumansModels, MolecularMolecular StructureNuclear Receptor Coactivator 2Retinoid X Receptor alphaSpiro CompoundsFuransNCOA2 protein, humanNuclear Receptor Coactivator 2Retinoid X Receptor alphaSpiro Compoundsspiroketaldrug designdrug discoverynatural productsspiro compoundsstructure elucidation

Identifiers

PMID28407400
PMCPMC5435924

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Registered trials

None linked

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.