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 Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Synthesis, crystal structure and Hirshfeld surface analysis of 2-(2,5-dioxo-4,4-di-phenyl-imidazolidin-1-yl)-<i>N</i>-(4-fluoro-phen-yl)acetamide (phenytoin analog).

Acta crystallographica. Section E, Crystallographic communications·2026
Same author

Structure-Guided Design of Proteomimetics Targeting the SARS-CoV-2 S-RBD/hACE2 Interface.

Journal of medicinal chemistry·2026
Same author

Profiling crystal engineered ligands for targeting treatment resistant androgen receptors.

bioRxiv : the preprint server for biology·2026
Same author

Androgen Receptor Point Mutations: A Mechanism of Therapeutic Resistance and a Framework for Rational Drug Design.

Cancers·2026
Same author

Adhesion G protein-coupled receptors.

Pharmacological reviews·2026
Same author

Profiling circular RNAs in amniotic fluid and fetal lungs from congenital diaphragmatic hernia cases: insights into potential prognostic and diagnostic applications.

Pediatric surgery international·2026

Related Experiment Video

Updated: Jan 9, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.8K

Structure-Guided Optimization of Selective Covalent Reversible Peptidomimetic Inhibitors Targeting TMPRSS6.

Walid Guerrab1, Matthieu Lepage1, Antoine Désilets1

  • 1Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.

Journal of Medicinal Chemistry
|December 5, 2025
PubMed
Summary

Researchers developed highly selective inhibitors for Transmembrane protease, serine 6 (TMPRSS6), crucial for iron regulation. This breakthrough utilizes a novel peptidomimetic design, offering a promising therapeutic strategy.

More Related Videos

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.5K
Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

12.9K

Related Experiment Videos

Last Updated: Jan 9, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.8K
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.5K
Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

12.9K

Area of Science:

  • Biochemistry
  • Drug Discovery
  • Protease Inhibition

Background:

  • Developing selective protease inhibitors is difficult due to similar catalytic pockets.
  • Transmembrane protease, serine 6 (TMPRSS6) regulates iron homeostasis.
  • Matriptase shares structural similarities with TMPRSS6.

Purpose of the Study:

  • To develop selective inhibitors targeting TMPRSS6.
  • To exploit structural differences between TMPRSS6 and matriptase for inhibitor design.
  • To create potent and selective peptidomimetics for TMPRSS6.

Main Methods:

  • Optimization of ketobenzothiazole-based peptidomimetics using a P4-P3-P2-Arg-Kbt scaffold.
  • Structure-based design focusing on catalytic subpocket differences.
  • In vitro assays to assess potency and selectivity against TMPRSS6, matriptase, Factor Xa, and Thrombin.
  • Cell-based assays to confirm inhibitor efficacy.

Main Results:

  • A combination of bulky P4/P3 residues and polar P2 amino acids enhanced selectivity and potency.
  • WGU55 demonstrated exceptional selectivity for TMPRSS6 over matriptase.
  • WGU55 showed minimal off-target inhibition of coagulation proteases (Factor Xa, Thrombin).
  • Cell-based assays confirmed WGU55's high potency and selectivity.

Conclusions:

  • A rational design strategy for selective TMPRSS6 inhibition was validated.
  • Peptidomimetics offer a promising approach for developing targeted TMPRSS6 therapeutics.
  • WGU55 represents the most selective TMPRSS6 inhibitor identified to date.