Development of the first internally-quenched fluorescent substrates of human cathepsin C: The application in the enzyme detection in biological samples

Łęgowska, Anna; Hamon, Yveline; Wojtysiak, Anna; Grzywa, Renata; Sieńczyk, Marcin; Burster, Timo; Korkmaz, Brice; Lesner, Adam

doi:10.1016/j.abb.2016.10.007

Cited by 13 publications

(10 citation statements)

References 52 publications

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“…Pro-CatC secreted by bronchial cells and resident alveolar macrophages is found in lung secretions from healthy individuals. However, CatC activity is detected in the lung secretions of patients suffering a chronic inflammatory lung diseases such as cystic fibrosis or asthma dominated by a neutrophilic inflammation (Hamon, Legowska, et al, 2016b;Legowska, et al, 2016). The enzyme concentration correlates with neutrophil numbers, which has also been experimentally confirmed in bronco-alveolar lavage fluid of macaques after lipopolysachharride-induced lung inflammation.…”

Section: Subcellular Localization and Secretionmentioning

confidence: 79%

“…The S1' site is rather shallow. Beyond the S2' site, the active site cleft area is wide open, indicating that there is no particular site defined for the binding of substrate residues (Legowska, et al, 2016).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Selective and sensitive fluorescence resonance energy transfer peptides were recently developed to measure human CatC activity (Legowska, et al, 2016). Two series of tetra-and pentapeptide substrates were synthesized allowing to study the S′ specificity of CatC.…”

Section: Proteolytic Activity Detectionmentioning

confidence: 99%

“…Two series of tetra-and pentapeptide substrates were synthesized allowing to study the S′ specificity of CatC. The highly specific substrate Thi-Ala(Mca)-Ser-Gly-Tyr(3-NO 2 )-NH 2 was selected for the detection of CatC activity in complex biological samples such as cell lysates, urine and bronchoalveolar lavage fluids (Legowska, et al, 2016).…”

Section: Proteolytic Activity Detectionmentioning

confidence: 99%

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Therapeutic targeting of cathepsin C: from pathophysiology to treatment

Korkmaz¹,

Caughey²,

Chapple³

et al. 2018

Pharmacology & Therapeutics

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Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects mediated by these proteases in inflammatory/auto-immune disorders. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome (PLS). The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials.

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Section: Subcellular Localization and Secretionmentioning

confidence: 79%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Proteolytic Activity Detectionmentioning

confidence: 99%

Section: Proteolytic Activity Detectionmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic targeting of cathepsin C: from pathophysiology to treatment

Korkmaz¹,

Caughey²,

Chapple³

et al. 2018

Pharmacology & Therapeutics

Self Cite

View full text Add to dashboard Cite

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“…Currently, only a very limited number of studies have been devoted to the development of synthetic substrates for certain types of cysteine peptidases. Therefore, substrates were developed for cathepsin B (Cezari et al, 2002;Ruzza et al, 2006), cathepsin L (Puzer et al, 2004;Lęgowska et al, 2014), cathepsin C (Lęgowska et al, 2016), and cathepsin V (Puzer et al, 2004) activities, but all are also non-selective.…”

Section: Discussionmentioning

confidence: 99%

New Glutamine-Containing Substrates for the Assay of Cysteine Peptidases From the C1 Papain Family

Filippova

Dvoryakova

Sokolenko

et al. 2020

Front. Mol. Biosci.

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New substrates with glutamine in the P1-position are introduced for the assay of peptidases from the C1 papain family, with a general formula of Glp-Phe-Gln-X, where Glp is pyroglutamyl and X is pNA (p-nitroanilide) or AMC (4-amino-7-methylcoumaride). The substrates have a simple structure, and C1 cysteine peptidases of various origins cleave them with high efficiency. The main advantage of the substrates is their selectivity for cysteine peptidases of the C1 family. Peptidases of other clans, including serine trypsin-like peptidases, do not cleave glutamine-containing substrates. We demonstrate that using Glp-Phe-Gln-pNA in combination with a commercially available substrate, Z-Arg-Arg-pNA, provided differential determination of cathepsins L and B. In terms of specific activity and kinetic parameters, the proposed substrates offer improvement over the previously described alanine-containing prototypes. The efficiency and selectivity of the substrates was demonstrated by the example of chromatographic and electrophoretic analysis of a multi-enzyme digestive complex of stored product pests from the Tenebrionidae family.

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Planarian regeneration in space: Persistent anatomical, behavioral, and bacteriological changes induced by space travel

et al. 2017

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Regeneration is regulated not only by chemical signals but also by physical processes, such as bioelectric gradients. How these may change in the absence of the normal gravitational and geomagnetic fields is largely unknown. Planarian flatworms were moved to the International Space Station for 5 weeks, immediately after removing their heads and tails. A control group in spring water remained on Earth. No manipulation of the planaria occurred while they were in orbit, and space‐exposed worms were returned to our laboratory for analysis. One animal out of 15 regenerated into a double‐headed phenotype—normally an extremely rare event. Remarkably, amputating this double‐headed worm again, in plain water, resulted again in the double‐headed phenotype. Moreover, even when tested 20 months after return to Earth, the space‐exposed worms displayed significant quantitative differences in behavior and microbiome composition. These observations may have implications for human and animal space travelers, but could also elucidate how microgravity and hypomagnetic environments could be used to trigger desired morphological, neurological, physiological, and bacteriomic changes for various regenerative and bioengineering applications.

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Development of the first internally-quenched fluorescent substrates of human cathepsin C: The application in the enzyme detection in biological samples

Cited by 13 publications

References 52 publications

Therapeutic targeting of cathepsin C: from pathophysiology to treatment

Therapeutic targeting of cathepsin C: from pathophysiology to treatment

New Glutamine-Containing Substrates for the Assay of Cysteine Peptidases From the C1 Papain Family

Planarian regeneration in space: Persistent anatomical, behavioral, and bacteriological changes induced by space travel

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