Preclinical evaluation of alpha-1-proteinase inhibitor

Fournel, Michael A.; Newgren, James O.; Betancourt, Carmen M.; Irwin, Russell G.

doi:10.1016/s0002-9343(88)80069-x

Cited by 8 publications

(2 citation statements)

References 8 publications

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“…Although uncommon, chronic use may lead to both local and systemic complications, 19,20 ranging from tissue atrophy to life‐threatening adrenal crisis. In contrast, intravenous administration of AAT derived from human plasma has been used for hereditary AAT deficiency for decades with a very favorable safety profile 21 . Although there is less data on the systemic safety of ilomastat, both favorable systemic and local tissue response responses have been observed 22,23 .…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Proteases in Chronic Otitis Externa

Antonelli

Schultz

Cantwell³

et al. 2005

The Laryngoscope

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Section: Discussionmentioning

confidence: 99%

Inflammatory Proteases in Chronic Otitis Externa

Antonelli

Schultz

Cantwell³

et al. 2005

The Laryngoscope

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“…Neutrophil elastase is implicated as a major contributor to tissue damage in both acute and chronic inflammatory processes (Sandborg et al, 1988;Travis, 1988) and has therefore been targeted by many researchers for development of potent and specific inhibitors (Bonney et al, 1989;Hassall et al, 1985;Nick et al, 1988;Fournel et al, 1988;Trainor, 1987). Many of the most effective of the low molecular weight inhibitors reported in the literature have both hydrophobic and anionic substituents which appear to enhance both specificity and binding affinity (Harper et al, 1985;Doherty et al, 1986;Lentini et al, 1987;Cook & Ternai, 1988).…”

Section: Discussionmentioning

confidence: 99%

Inhibitors directed to binding domains in neutrophil elastase

Tyagi¹,

Simon²

1990

Biochemistry

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Human neutrophil elastase (HNE) can be inhibited by unsaturated fatty acids, including oleic acid [Ashe, B. M., & Zimmerman, M. (1977) Biochem. Biophys. Res. Commun. 75, 194-199; Cook, L., & Ternai, B. (1988) Biol. Chem. Hoppe-Seyler 369, 627-631], but is not affected by saturated fatty acids. We have shown that the interaction of oleic acid with HNE can be characterized by two apparent inhibitory modes: a high-affinity mode (Ki = 48 +/- 3 nM), resulting in partial noncompetitive inhibition (87% residual activity), and a competitive inhibitory mode of lower affinity (Ki = 16 +/- 1 microM). Binding of oleate in the high-affinity mode induces a blue shift in the endogenous fluorescence arising from the tryptophan residues in HNE. This shift is maximal in the presence of 1 microM oleate; higher concentrations of fatty acid have no further effect on the fluorescence spectrum. The negatively charged fluorescent ester of oleic acid and hydroxypyrenetrisulfonate (HPTSoleate) interacts with HNE at an apparent single site (Ki = 44 +/- 3 nM), resulting in competitive inhibition. A blue shift in the emission maximum of the pyrene fluorescence at 410 nm and a decrease in the ratio of the intensities of the maximum at 388 and 410 nm indicate that upon binding to HNE the environment of the pyrene ring in HPTSoleate becomes more hydrophobic.(ABSTRACT TRUNCATED AT 250 WORDS)

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