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

Gsalpha-selective G protein antagonists

M Hohenegger1, M Waldhoer, W Beindl

  • 1Institute of Pharmacology, University of Vienna, Währinger Strasse 13a, A-1090 Austria.

Proceedings of the National Academy of Sciences of the United States of America
|February 21, 1998
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

Allosteric modulators of solute carrier function: a theoretical framework.

Frontiers in physiology·2023
Same author

Enhancement of awareness through feedback does not lead to interlimb transfer of obstacle crossing in virtual reality.

Journal of biomechanics·2023
Same author

Obstacle avoidance training in virtual environments leads to limb-specific locomotor adaptations but not to interlimb transfer in healthy young adults.

Journal of biomechanics·2021
Same author

The importance of laboratory re-evaluation in cases of suspected child abuse - A case report.

Legal medicine (Tokyo, Japan)·2017
Same author

Response to Black R and Chin R's letter on our article "Epilepsy in children and adolescents: Disease concepts, practical knowledge, and coping".

Epilepsy & behavior : E&B·2016
Same author

Late-onset palsy of the recurrent laryngeal nerve after thyroid surgery.

The British journal of surgery·2014
Same journal

Chemotactic self-organization captures the dynamics of mammalian hair follicle patterning.

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

Tomographic imaging of superconducting order using particle-hole interference.

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

Inhibitory potential of autologous neutralizing antibodies sets quantitative limits on the rebound-competent HIV-1 reservoir.

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

Inferring epidemiological parameters under an infectious phylogeography model with visitor dynamics.

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

Analytical modeling for suction cup designs for skin-interfaced wearable devices.

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

Improving cell-free metabolism through direct integration of artificial respiratory chains.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Researchers identified NF449 and NF503 as selective inhibitors of Gsalpha, a key G protein. These compounds offer a novel approach for targeting specific G protein pathways in research and drug development.

Area of Science:

  • Biochemistry
  • Molecular Pharmacology
  • Signal Transduction

Background:

  • G protein activation involves GDP/GTP exchange on the Galpha subunit.
  • Suramin inhibits G protein activation but lacks subtype selectivity.
  • Developing subtype-selective G protein inhibitors is crucial for precise pharmacological intervention.

Purpose of the Study:

  • To identify novel analogues that selectively inhibit the stimulatory G protein alpha subunit (Gsalpha).
  • To characterize the selectivity profile of identified compounds against other G protein alpha subunits.
  • To demonstrate the feasibility of achieving subtype-selective G protein inhibition.

Main Methods:

  • Screening for compounds that inhibit guanosine 5 zost-[gamma-thio]triphosphate ([35S]GTP[gammaS]) binding to Gsalpha.

Related Experiment Videos

  • Assessing the inhibition of adenylyl cyclase activity in Gsalpha-deficient membranes.
  • Evaluating the disruption of receptor-G protein coupling (beta-adrenergic receptor/Gs).
  • Testing selectivity against Gi/Go-coupled (A1-adenosine receptor) and Gq-coupled (angiotensin II type-1 receptor) pathways.

    • Main Results:

    • Two selective Gsalpha inhibitors, NF449 and NF503, were identified.
    • These compounds selectively suppressed [35S]GTP[gammaS] binding to Gsalpha but not Gialpha-1.
    • NF449 and NF503 inhibited Gsalpha-mediated adenylyl cyclase activity and beta-adrenergic receptor/Gs coupling in the low micromolar range.
    • Significant selectivity was observed, with minimal effects on Gi/Go and Gq-coupled receptors at effective Gsalpha-inhibiting concentrations.

    Conclusions:

    • NF449 and NF503 are potent and selective antagonists of Gsalpha.
    • These compounds effectively disrupt beta-adrenergic receptor/Gs coupling.
    • The findings validate the strategy of developing subtype-selective G protein inhibitors for targeted signaling modulation.