Targeting COPD: advances on low-molecular-weight inhibitors of human neutrophil elastase

2011 ◽  
Vol 33 (S1) ◽  
pp. E73-E101 ◽  
Author(s):  
Susana D. Lucas ◽  
Elsa Costa ◽  
Rita C. Guedes ◽  
Rui Moreira
Keyword(s):  
Molecular Weight ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Low Molecular Weight ◽  
Human Neutrophil Elastase

Elastin-derived peptide binding to a hydrophobic domain on neutrophil elastase

1994 ◽  
Vol 72 (9-10) ◽  
pp. 419-427 ◽  
Author(s):  
Suresh C. Tyagi ◽  
Sanford R. Simon
Keyword(s):  
Molecular Weight ◽  
Neutrophil Elastase ◽  
Protein Fraction ◽  
Competitive Inhibition ◽  
Hydrophobic Interactions ◽  
Human Aorta ◽  
Low Molecular Weight ◽  
Human Neutrophil Elastase ◽  
Amidolytic Activity ◽  
Hydrophobic Domain

To understand the contributions of binding of elastin to domains removed from the active site of neutrophil elastase, we isolated an elastin-derived peptide (EDP) fraction, which we have previously shown was tightly linked to neutrophil elastase after prolonged digestion of elastin but which can be released from the enzyme with hydroxylamine. Elastin from human aorta was incubated with human neutrophil elastase under conditions favoring proteolysis. Low molecular weight species, including free EDP, were separated from the protein fraction by a small centrifuged gel filtration column. The high molecular weight protein fraction was subjected directly to 0.5 M hydroxylamine. The reaction mixture was then fractionated on a phosphocellulose column using an ionic gradient. A fraction was collected that exhibited fluorescence with a peak at ~410 nm when excited at 320 nm, indicating the presence of desmosine and (or) isodesmosine. A second peak with amidolytic activity towards methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroaniline (MeOSucAAPVpNa), but no fluorescence at 410 nm was also detected at the same elution volume where free elastase appeared. After removal of low molecular weight digestion products but prior to treatment with hydroxylamine, the putative elastase–EDP complex possessed no amidolytic activity towards MeOSucAAPVpNa. When the liberated EDP was added to elastase in an amidolytic assay, the EDP behaved as only a partial noncompetitive inhibitor [Formula: see text], but bound with high affinity to neutrophil elastase [Formula: see text], as detected by its ability to quench elastase endogenous fluorescence. The complete emission spectrum of the mixture of elastase and EDP obtained at excitation wavelengths specific for tryptophan and desmosine/isodesmosine suggests that the EDP was in a hydrophobic environment which was close to at least one of the three tryptophan residues in the enzyme. Based on fluorescence energy transfer, we have estimated a distance between the elastase and EDP of ~10 ± 3 Å (1 Å = 0.1 nm) during elastinolysis. This pattern of binding to a hydrophobic site on neutrophil elastase without competitive inhibition of amidolytic activity was consistent with the importance of hydrophobic interactions between neutrophil elastase and elastin within a region of the enzyme removed from the active site.Key words: proteinase, elastase, elastin, extracellular matrix, elastin-derived peptide.

scholarly journals Flavonoids as inhibitors of human neutrophil elastase

2021 ◽  
Vol 36 (1) ◽  
pp. 1016-1028
Author(s):  
Katarzyna Jakimiuk ◽  
Jakub Gesek ◽  
Atanas G. Atanasov ◽  
Michał Tomczyk
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase

Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl Ketones

1994 ◽  
Vol 37 (26) ◽  
pp. 4538-4553 ◽  
Author(s):  
Michael R. Angelastro ◽  
Larry E. Baugh ◽  
Philippe Bey ◽  
Joseph P. Burkhart ◽  
Teng-Man Chen ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase ◽  
Orally Active

Optimisation of a human neutrophil elastase assay and investigation of the effect of sesquiterpene lactones

Biologicals ◽  
2005 ◽  
Vol 33 (3) ◽  
pp. 175-184 ◽  
Author(s):  
Karin Schorr ◽  
Anita Rott ◽  
FernandoBatista Da Costa ◽  
Irmgard Merfort
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Sesquiterpene Lactones ◽  
Human Neutrophil Elastase

scholarly journals Elastase as a marker for neutrophilic myeloid cells.

1984 ◽  
Vol 32 (4) ◽  
pp. 389-394 ◽  
Author(s):  
J A Kramps ◽  
P van der Valk ◽  
M M van der Sandt ◽  
J Lindeman ◽  
C J Meijer
Keyword(s):  
Cell Lines ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Myeloid Cells ◽  
Hematopoietic Cell ◽  
Human Neutrophil Elastase ◽  
Specific Marker ◽  
Neoplastic Cells ◽  
Myeloproliferative Diseases ◽  
Myelomonocytic Leukemia

The immunohistochemical results obtained with antibodies directed against human neutrophil elastase is described. It was found that neutrophil elastase can be used as a specific marker of cells of the neutrophilic lineage. In normal hematopoietic cell preparations, only promyelocytes and more differentiated myeloid cells stain positive for elastase. In acute or chronic myeloid and myelomonocytic leukemia, the same neutrophil myeloid cells stain positive, whereas neoplastic cells of the monocytoid line are negative. Using elastase in conjunction with other markers, it is possible to differentiate easily the involvement of different cell lines in myeloproliferative diseases.

Sign in / Sign up

Export Citation Format

Share Document