Human leukocyte elastase plays a crucial role in a variety of inflammatory disorders and represents an important subject of biomedical studies. The chemotype of peptidic phosphonates was employed for the design of a new activity-based probe for human leukocyte elastase. Its structure combines the phosphonate warhead with an adequate peptide portion and a BODIPY fluorophore with a clickable ethinylphenyl moiety at position. The probe was assembled by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition. It was characterized as an active site-directed elastase inhibitor exhibiting a second-order rate constant of inactivation of 88400 Ms. The suitability of as a fluorescent probe for human leukocyte elastase was demonstrated by in-gel fluorescence analysis. Labeling experiments and inhibition data toward a panel of related proteases underlined the selectivity of the probe for the targeted leukocyte elastase.
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http://dx.doi.org/10.1021/acsmedchemlett.7b00533 | DOI Listing |
Nat Commun
January 2025
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Corticosteroid binding globulin (CBG; SERPINA6) binds >85% of circulating glucocorticoids but its influence on their metabolic actions is unproven. Targeted proteolytic cleavage of CBG by neutrophil elastase (NE; ELANE) significantly reduces CBG binding affinity, potentially increasing 'free' glucocorticoid levels at sites of inflammation. NE is inhibited by alpha-1-antitrypsin (AAT; SERPINA1).
View Article and Find Full Text PDFSci Rep
December 2024
Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
The lungs of people with cystic fibrosis (PwCF) are characterized by recurrent bacterial infections and inflammation. Infections in cystic fibrosis (CF) are left unresolved despite excessive neutrophil infiltration. The role of CFTR in neutrophils is not fully understood.
View Article and Find Full Text PDFWiad Lek
December 2024
BUKOVINIAN STATE MEDICAL UNIVERSITY, CHERNIVTSI, UKRAINE.
Objective: Aim: To study the peculiarities of food tolerance disorders in premature infants, taking into account the risk factors of gestational age and maternal labor, the peculiarities of the course of perinatal pathology, in order to determine pathogenetically sound clinical and laboratory criteria.
Patients And Methods: Materials and Methods: A comprehensive clinical and laboratory evaluation was performed on 67 preterm infants of gestational age 32 to 33/6 weeks with severe food tolerance disorders in perinatal pathology. The comparison group consisted of 31 newborns with gestational age of 34 to 37 weeks.
Clin Chim Acta
February 2025
Department of Medicine, University of Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia; Endocrine and Diabetes Services, The Queen Elizabeth Hospital, Australia.
Background: Corticosteroid-binding globulin (CBG) modulates tissue cortisol availability via modification of cortisol:CBG binding affinity in response to multiple factors, including neutrophil elastase (NE) cleavage of the reactive centre loop (RCL), converting high affinity CBG (haCBG) to low affinity CBG (laCBG). In vitro, glycosylation of the RCL at Asn347 affects NE cleavage susceptibility. To date, no direct measurement of laCBG, which would verify NE cleavage, has been reported.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Children's Hospital of Richmond at VCU, Richmond, VA 23298, USA.
Neutrophil elastase (NE) has been reported to be a pro-inflammatory stimulus for macrophages. The aim of the present study was to determine the impact of NE exposure on the human macrophage proteome and evaluate its impact on pro-inflammatory signals. Human blood monocytes from healthy volunteers were differentiated to macrophages and then exposed to either 500 nM of NE or control vehicle for 2 h in triplicate.
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