Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Designed Spiroketal Protein Modulation.

Marcel Scheepstra1, Sebastian A Andrei1, M Yagiz Unver2

  • 1Laboratory 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.

Angewandte Chemie (International Ed. in English)
|April 14, 2017
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Targeting the Energy-Coupling Factor Transporters: A Novel Antibiotic Drug Target in <i><i>Streptococcus pneumoniae</i></i>.

Journal of medicinal chemistry·2026
Same author

Hit-to-Lead Optimization of Energy-Coupling Factor (ECF) Transporter Inhibitors as Novel Antibiotic.

Journal of medicinal chemistry·2026
Same author

Cytochrome P450-Mediated Metabolism of Antimycobacterial <i>N</i>α-Aroyl-<i>N</i>-aryl-phenylalanine Amides.

ACS infectious diseases·2026
Same author

Identification of DksA as a novel pro-inflammatory mediator of <i>Pseudomonas aeruginosa</i> under conditions mimicking chronic cystic fibrosis lung infection.

Virulence·2026
Same author

Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Identification of Natural-Product Inhibitors of the 2<i>C</i>‑Methyl‑d‑erythritol 4‑Phosphate Pathway.

ACS medicinal chemistry letters·2026
Same journal

Fundamentals, Measurement and Regulation of the Conductance of Single Molecule Junctions.

Angewandte Chemie (International ed. in English)·2026
Same journal

Quantitative Photoswitching of Spin States in o-Fluoroazobenzene-Loaded Metal-Organic Frameworks.

Angewandte Chemie (International ed. in English)·2026
Same journal

Cobalt Nanoparticles Confined in Defective Carbon Matrices for Robust Intermittent CO<sub>2</sub> Methanation.

Angewandte Chemie (International ed. in English)·2026
Same journal

Copper(II/III) Redox Couple Enables C─H Methylation via a Radical Mechanism Analogous to SAM Enzymes.

Angewandte Chemie (International ed. in English)·2026
Same journal

Ring Strain Engineering of Cyclic Ethers for High-Performance Sodium Metal Batteries.

Angewandte Chemie (International ed. in English)·2026
Same journal

Bond Length as a Unified Descriptor for Stable Iodine Battery.

Angewandte Chemie (International ed. in English)·2026
See all related articles

Researchers designed a novel bisbenzannulated spiroketal that binds strongly to the retinoid X receptor (RXR). This spiroketal shows potential for structure-based drug discovery targeting nuclear receptors.

Area of Science:

  • Medicinal Chemistry
  • Structural Biology
  • Drug Discovery

Background:

  • Spiroketals are prevalent structural motifs in biologically active natural products.
  • Their synthesis is well-studied, yet their application in structure-based drug discovery, particularly bisbenzannulated spiroketals, remains undemonstrated.
  • Retinoid X Receptor (RXR) is a key target in various therapeutic areas.

Purpose of the Study:

  • To rationally design a bisbenzannulated spiroketal with potent binding affinity for RXR.
  • To investigate the mechanism of action and structural basis for the spiroketal's interaction with RXR.
  • To explore the potential of designed spiroketals in targeting nuclear receptor subtypes.

Main Methods:

  • Rational design of a bisbenzannulated spiroketal compound.
Keywords:
drug designdrug discoverynatural productsspiro compoundsstructure elucidation

Related Experiment Videos

  • Biochemical assays to determine binding affinity to retinoid X receptor (RXR).
  • X-ray crystallography to solve the ternary complex structure of spiroketal-hRXRα-TIF2.

    • Main Results:

    • A novel bisbenzannulated spiroketal was successfully designed and synthesized.
    • The designed spiroketal demonstrated potent binding to RXR and induced partial co-activator recruitment.
    • The crystal structure revealed a canonical allosteric mechanism underlying the partial agonism.

    Conclusions:

    • Designed spiroketals, including bisbenzannulated variants, can effectively target nuclear receptors like RXR.
    • The first co-crystal structure of a designed spiroketal-protein complex provides insights into spiroketal-mediated allosteric modulation.
    • This study validates spiroketals as a promising scaffold for structure-based drug discovery against nuclear receptor targets.