PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10397497

A substrate combinatorial array for caspases.

D Lee·J L Adams·M Brandt·W E DeWolf·P M Keller·M A Levy
View original source ↗Export metadata ↓

Abstract

An efficient strategy for the synthesis of a tetrapeptidyl substrate combinatorial array directed toward the caspases is described. Testing of this array with caspases 1 and 4 gave substrate hydrolytic profiles characteristic of each caspase, and permitted the identification of efficiently processed substrates. A comparison of this approach to that using a positional scanning library is presented.

Explore related subjects

Caspase 1CaspasesCaspases, InitiatorCatalysisKineticsOligopeptidesSubstrate SpecificityJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D Lee, J L Adams, M Brandt, W E DeWolf, P M Keller, M A Levy. 1999-06-21. A substrate combinatorial array for caspases.. https://doi.org/10.1016/s0960-894x(99)00260-7

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2001

Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells.

Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcepsilonRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcepsilonRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcepsilonRI on LLDC derived from atopic dermatitis patients that express high levels of FcepsilonRI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumulation of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL-16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of FcepsilonRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcepsilonRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.

Caspase 1↗
PubMed2001

Structure-based design of caspase-1 inhibitor containing a diphenyl ether sulfonamide.

A series of compounds was designed and prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase-1. These inhibitors, which employ a diphenyl ether sulfonamide, were designed to improve potency by forming favorable interactions between the diphenyl ether rings and the prime side hydrophobic region. An X-ray crystal structure of a representative member of the diphenyl ether sulfonamide series bound to the active site of caspase-1 was obtained.

Caspase 1↗
PubMed2001

T cells enhance production of IL-18 by monocytes in response to an intracellular pathogen.

We studied the effect of T cells on IL-18 production by human monocytes in response to Mycobacterium tuberculosis. Addition of activated T cells markedly enhanced IL-18 production by monocytes exposed to M. tuberculosis. This effect was mediated by a soluble factor and did not require cell-to-cell contact. The effect of activated T cells was mimicked by recombinant IFN-gamma and was abrogated by neutralizing Abs to IFN-gamma. IFN-gamma also enhanced the capacity of alveolar macrophages to produce IL-18 in response to M. tuberculosis, suggesting that this mechanism also operates in the lung during mycobacterial infection. IFN-gamma increased IL-18 production by increasing cleavage of pro-IL-18 to mature IL-18, as it enhanced caspase-1 activity but did not increase IL-18 mRNA expression. These findings suggest that activated T cells can contribute to the initial immune response by augmenting IL-18 production by monocytes in response to an intracellular pathogen.

Caspase 1↗