Proteinase 3 phosphonic inhibitors

Grzywa, Renata; Lesner, Adam; Korkmaz, Brice; Sieńczyk, Marcin

doi:10.1016/j.biochi.2019.03.005

Cited by 8 publications

(7 citation statements)

References 63 publications

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“…The balance between serine proteases and their inhibitors seems to play a crucial role in maintaining the gut homeostasis and may constitute a potential target to develop new therapeutics 8 . In this context, significant efforts have been recently made to design and assess new selective inhibitors for specific serine proteases known to be involved in IBD 168,169 . Further studies on this subject will provide additional mechanistic insights regarding the role of serine protease within the gut.…”

Section: Achieving Specificity: Tools Assessing Serine Protease Activmentioning

confidence: 99%

“…8 In this context, significant efforts have been recently made to design and assess new selective inhibitors for specific serine proteases known to be involved in IBD. 168,169 Further studies on this subject will provide additional mechanistic insights regarding the role of serine protease within the gut.…”

Section: Tools Assessing Serine Protease Activit Y and Their Application In The Gutmentioning

confidence: 99%

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Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

et al. 2020

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Serine proteases have been long recognized to coordinate many physiological processes and play key roles in regulating the inflammatory response. Accordingly, their dysregulation has been regularly associated with several inflammatory disorders and suggested as a central mechanism in the pathophysiology of digestive inflammation. So far, studies addressing the proteolytic homeostasis in the gut have mainly focused on host serine proteases as candidates of interest, while largely ignoring the potential contribution of their bacterial counterparts. The human gut microbiota comprises a complex ecosystem that contributes to host health and disease. Yet, our understanding of microbially produced serine proteases and investigation of whether they are causally linked to IBD is still in its infancy. In this review, we highlight recent advances in the emerging roles of host and bacterial serine proteases in digestive inflammation. We also discuss the application of available tools in the gut to monitor disease‐related serine proteases. An exhaustive representation and understanding of such functional potential would help in closing existing gaps in mechanistic knowledge.

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Section: Achieving Specificity: Tools Assessing Serine Protease Activmentioning

confidence: 99%

Section: Tools Assessing Serine Protease Activit Y and Their Application In The Gutmentioning

confidence: 99%

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

et al. 2020

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“…Although the roles of PR3 and CG in lung disease have been discussed in the literature [ 71 ], and specific PR3 and CG inhibitors described [ 72 , 73 ], there are no clinical trials exploring the roles of these specific inhibitors in lung disease.…”

Section: Current Evidence For Protease Inhibitors In Chronic Lung Diseasementioning

confidence: 99%

The emerging role of proteases in α₁-antitrypsin deficiency and beyond

Fazleen

Wilkinson

2021

ERJ Open Res

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α1-Antitrypsin deficiency (AATD) has been historically under-recognised and under-diagnosed; recently it has begun to receive greater interest in terms of attempts at deeper elucidation of pathology and treatment options. However, the concept of disease phenotypes within AATD (emphysema, chronic bronchitis, bronchiectasis or a combination of phenotypes) has not been proposed or studied. Of the three neutrophil serine proteases, neutrophil elastase was historically believed to be the sole contributor to disease pathology in AATD. Recently, Proteinase-3 has been increasingly studied as an equal, if not greater, contributor to the disease process. Cathepsin G, however, has not been extensively evaluated in this area. Matrix metalloproteinases have also been mentioned in the pathogenesis of AATD but have not been widely explored. This article considers the available evidence for differential protease activity in patients with AATD, including the contribution to distinct phenotypes of the disease. Owing to limited literature in this area, extrapolations from studies of other chronic lung diseases with similar phenotypes, including COPD and bronchiectasis, have been made. We consider a new framework of understanding defined by protease-driven endotypes of disease which may lead to new opportunities for precision medicine.

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“…When activated, neutrophils release several mediators, including neutrophil serine proteases (NSPs) such as cathepsin G (CatG), protease 3 (PR3), neutrophil elastase (NE), and neutrophil serine protease 4 (NSP4) (Korkmaz et al, 2008). The ABP, composed of the recognition sequence Bt-Val-Tyr-Asp-nVal P (O-C 6 H 4 -4-Cl) 2 , which is an α-aminoalkylphosphonate diaryl ester derivative and harbors a biotin tag, labels PR3 (Grzywa et al, 2019). Alternatively, the sulfonyloxyphthalimide moiety warhead with a peptide linker and a coumarin fluorophore for in-gel fluorescent detection can be used to detect porcine pancreatic elastase.…”

Section: Abps and Their Applications To Analyze Serine Proteasesmentioning

confidence: 99%

Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples

et al. 2021

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Neutrophils, migrating to the site of infection, are able to release serine proteases after being activated. These serine proteases comprise cathepsin G (CatG), neutrophil elastase protease 3 (PR3), and neutrophil serine protease 4 (NSP4). A disadvantage of the uncontrolled proteolytic activity of proteases is the outcome of various human diseases, including cardiovascular diseases, thrombosis, and autoimmune diseases. Activity-based probes (ABPs) are used to determine the proteolytic activity of proteases, containing a set of three essential elements: Warhead, recognition sequence, and the reporter tag for detection of the covalent enzyme activity–based probe complex. Here, we summarize the latest findings of ABP-mediated detection of proteases in both locations intracellularly and on the cell surface of cells, thereby focusing on CatG. Particularly, application of ABPs in regular flow cytometry, imaging flow cytometry, and mass cytometry by time-of-flight (CyTOF) approaches is advantageous when distinguishing between immune cell subsets. ABPs can be included in a vast panel of markers to detect proteolytic activity and determine whether proteases are properly regulated during medication. The use of ABPs as a detection tool opens the possibility to interfere with uncontrolled proteolytic activity of proteases by employing protease inhibitors.

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Proteinase 3 phosphonic inhibitors

Cited by 8 publications

References 63 publications

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

The emerging role of proteases in α₁-antitrypsin deficiency and beyond

Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples

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Proteinase 3 phosphonic inhibitors

Cited by 8 publications

References 63 publications

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

The emerging role of proteases in α1-antitrypsin deficiency and beyond

Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples

Contact Info

Product

Resources

About

The emerging role of proteases in α₁-antitrypsin deficiency and beyond