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

Adverse events of SARS-CoV-2 vaccination in patients with inflammatory rheumatic disease during repeated vaccination: An observational cohort study.

Rheumatology international·2025
Same author

Biogenic polymer based patches for congenital cardiac surgery: future development of implants.

Frontiers in cardiovascular medicine·2025
Same author

[Joint pain: How to identify rheumatic cause?]

MMW Fortschritte der Medizin·2024
Same author

Human Neutrophil Elastase: Characterization of Intra- vs. Extracellular Inhibition.

International journal of molecular sciences·2024
Same author

Inflammatory Back Pain and Psoriasis: Expecting Spondyloarthritis, Discovering Lymphoma.

Cureus·2024
Same author

Mast cell chymase suppresses functional parameters in primary human airway smooth muscle cells.

Allergy·2024

Related Experiment Video

Updated: Jul 24, 2025

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

11.4K

E-64c-Hydrazide Based Cathepsin C Inhibitors: Optimizing the Interactions with the S1'-S2' Area.

Nora Tromsdorf1, Fabian T H Ullrich2, Markus Rethmeier3

  • 1Fakultät für Chemie, Hochschule Aalen, Beethovenstraße 1, 73430, Aalen, Germany.

Chemmedchem
|July 10, 2023
PubMed
Summary

Inhibiting cathepsin C, a key enzyme in inflammatory diseases like COPD, can be achieved with a novel covalent inhibitor. This new drug effectively blocks neutrophil elastase activation in cell models.

Keywords:
DPPIE-64ccombinatorial chemistrycysteine proteaseneutrophil elastase

More Related Videos

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
19:16

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

Published on: March 17, 2010

20.7K
Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
11:44

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities

Published on: October 2, 2018

12.6K

Related Experiment Videos

Last Updated: Jul 24, 2025

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

11.4K
The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis
19:16

The Importance of Correct Protein Concentration for Kinetics and Affinity Determination in Structure-function Analysis

Published on: March 17, 2010

20.7K
Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
11:44

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities

Published on: October 2, 2018

12.6K

Area of Science:

  • Biochemistry
  • Pharmacology
  • Immunology

Background:

  • Neutrophil serine proteases (elastase, proteinase 3, cathepsin G) are activated by cathepsin C, contributing to inflammatory disorders like COPD.
  • Cathepsin C inhibition presents a therapeutic strategy for neutrophil-driven inflammatory conditions.

Purpose of the Study:

  • To optimize a covalent cathepsin C inhibitor for enhanced affinity and selectivity.
  • To investigate the S1'-S2' area of the inhibitor for improved ligand binding.

Main Methods:

  • Development of a covalent cathepsin C inhibitor based on E-64c-hydrazide.
  • Combinatorial approach to explore the S1'-S2' binding region.
  • Utilized U937 neutrophil precursor cell line for in vitro testing.

Main Results:

  • Identified Nle-tryptamide as a superior ligand for the S1'-S2' area compared to Leu-isoamylamide.
  • The optimized inhibitor effectively blocked intracellular cathepsin C activity in U937 cells.
  • Demonstrated suppression of neutrophil elastase activation by the inhibitor.

Conclusions:

  • A novel, optimized covalent cathepsin C inhibitor demonstrates potential for treating inflammatory diseases.
  • The inhibitor successfully targets cathepsin C, reducing downstream activation of key neutrophil proteases.
  • Further development of this inhibitor may offer a therapeutic avenue for COPD and related conditions.