ArticleThe Journal of biological chemistry2014
New selective peptidyl di(chlorophenyl) phosphonate esters for visualizing and blocking neutrophil proteinase 3 in human diseases.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Soluble Signal Inhibitory Receptor on Leukocytes-1 Is Released from Activated Neutrophils by Proteinase 3 Cleavage.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease.Frontiers in immunology · 2023Review
- Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters.Cellular and molecular life sciences : CMLS · 2022Article
- Novel inhibitors and activity-based probes targeting serine proteases.Frontiers in chemistry · 2022Article
- Iterative Optimization of the Cyclic Peptide SFTI-1 Yields Potent Inhibitors of Neutrophil Proteinase 3.ACS medicinal chemistry letters · 2019Article
- Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases.Cell chemical biology · 2019Article
- Recent Developments in Peptidyl Diaryl Phoshonates as Inhibitors and Activity-Based Probes for Serine Proteases.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Non-invasive profiling of protease-specific elastin turnover in lung cancer: biomarker potential.Journal of cancer research and clinical oncology · 2019Article
- Consequences of cathepsin C inactivation for membrane exposure of proteinase 3, the target antigen in autoimmune vasculitis.The Journal of biological chemistry · 2018Article
- A BODIPY-Tagged Phosphono Peptide as Activity-Based Probe for Human Leukocyte Elastase.ACS medicinal chemistry letters · 2018Article
- Pseudomonas aeruginosa proteolytically alters the interleukin 22-dependent lung mucosal defense.Virulence · 2017Article
- Toolbox of Fluorescent Probes for Parallel Imaging Reveals Uneven Location of Serine Proteases in Neutrophils.Journal of the American Chemical Society · 2017Article
- Emerging challenges in the design of selective substrates, inhibitors and activity-based probes for indistinguishable proteases.The FEBS journal · 2017Review
- [Analysis of salivary protease spectrum in chronic periodontitis].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2017Article
- Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases.The Journal of biological chemistry · 2016Article
- Neutrophil serine proteases exert proteolytic activity on endothelial cells.Kidney international · 2015Article
- Role of saliva proteinase 3 in dental caries.International journal of oral science · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of neutrophil protease 3 (PR3) is poorly understood despite of its role in autoimmune vasculitides and its possible involvement in cell apoptosis. This makes it different from its structural homologue neutrophil elastase (HNE). Endogenous inhibitors of human neutrophil serine proteases preferentially inhibit HNE and to a lesser extent, PR3. We constructed a single-residue mutant PR3 (I217R) to investigate the S4 subsite preferences of PR3 and HNE and used the best peptide substrate sequences to develop selective phosphonate inhibitors with the structure Ac-peptidyl(P)(O-C6H4-4-Cl)2. The combination of a prolyl residue at P4 and an aspartyl residue at P2 was totally selective for PR3. We then synthesized N-terminally biotinylated peptidyl phosphonates to identify the PR3 in complex biological samples. These inhibitors resisted proteolytic degradation and rapidly inactivated PR3 in biological fluids such as inflammatory lung secretions and the urine of patients with bladder cancer. One of these inhibitors revealed intracellular PR3 in permeabilized neutrophils and on the surface of activated cells. They hardly inhibited PR3 bound to the surface of stimulated neutrophils despite their low molecular mass, suggesting that the conformation and reactivity of membrane-bound PR3 is altered. This finding is relevant for autoantibody binding and the subsequent activation of neutrophils in granulomatosis with polyangiitis (formerly Wegener disease). These are the first inhibitors that can be used as probes to monitor, detect, and control PR3 activity in a variety of inflammatory diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.