Evidence map›Paper›PMID 34601876›Full record

ArticleJournal of medicinal chemistry2021

Blockade of GRTH/DDX25 Phosphorylation by Cyclic Peptides Provides an Avenue for Developing a Nonhormonal Male Contraceptive.

Murugananthkumar Raju, Raghuveer Kavarthapu, Rajakumar Anbazhagan, Sergio A Hassan, Maria L Dufau

Open access · greenAbstract read
In one paragraph

Article in 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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 50% of its field
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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

5 authors at 2 institutions in 1 country.

Murugananthkumar RajuSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, United States.
Raghuveer KavarthapuSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, United States.
Rajakumar AnbazhaganSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, United States.
Sergio A HassanBioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States.ORCID 0000-0003-3319-078X
Maria L DufauSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, United States.ORCID 0000-0002-3989-7113
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · US

Funding

Regulation of Hormone Receptors and Gonadal GenesZIAHD000150 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DUFAU, MARIA · 2009 to 2022
$15.9M
Hormone Receptors and Enzymes Regulating Gonadal and Mammary FunctionZ01HD000150 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DUFAU, MARIA · 1985 to 2008
$2.6M
Intramural NIH HHS Z01 HD000150Intramural NIH HHS ZIA HD000150
6 · The paper itself

Abstract

Gonadotropin-regulated testicular RNA helicase (GRTH)/DDX25 is a DEAD-box RNA helicase essential for the completion of spermatogenesis. Our previous studies indicated that blocking the GRTH phospho-site or perturbing the GRTH/protein kinase A (PKA) interface could provide an avenue for developing a nonhormonal male contraceptive. In this study, cyclic peptides were rationally designed and synthesized as promising therapeutic agents. The peptides showed effective delivery into COS-1 and germ cells and a dose-dependent inhibitory effect on GRTH phosphorylation. The peptides inhibit GRTH phosphorylation in the presence of PKA, and binding to the helicase resulted in thermal stabilization of non-phospho GRTH. Increased efficiency in fluorescence resonance energy transfer (FRET) assay revealed their interaction with GRTH. Cyclic peptide exposure of cultures from mice seminiferous tubules resulted in significant inhibition of phospho GRTH. These peptides did not exhibit toxicity. Effective delivery and targeted decrease of in vitro expression of phospho GRTH by cyclic peptides provide a promising angle to develop effective compounds as a nonhormonal male contraceptive.

Indexed as

Contraceptive Agents, MaleAnimalsChlorocebus aethiopsCOS CellsCyclic AMP-Dependent Protein KinasesDEAD-box RNA HelicasesDose-Response Relationship, DrugDrug DesignEnzyme InductionFluorescence Resonance Energy TransferMaleMicePeptides, CyclicPhosphorylationSeminiferous TubulesContraceptive Agents, MaleCyclic AMP-Dependent Protein KinasesDdx25 protein, mouseDEAD-box RNA HelicasesPeptides, Cyclic

Identifiers

PMID34601876
PMCPMC9446413
OpenAlexW3204282299

What OpenQuestion holds

Textmetadata
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Read underepoch 390

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.