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Abstract
Abstract:
Aims:
Certain cancers, pathogenic infections, and other diseases are facilitated by the host enzyme furin, a calcium-dependent serine protease that is the most prominent member of the family of proprotein convertases. Furin and the other proprotein convertases modify certain other proteins to change them from their inactive to active forms. Previous attempts to find an effective, non-toxic furin inhibitor to treat diseases facilitated by furin have had only limited success, due to toxicity or large molecular size that impedes absorption of the molecule. This has placed increased importance on the development of small-molecule furin inhibitors. The object of this study was to consider the effect of the noble gas xenon as a furin inhibitor.
Methods:
This study uses a fluorometric furin inhibition assay to compare the enzymatic activity of recombinant human furin after exposure to 99.999% xenon gas, compared to the enzymatic activity of untreated recombinant human furin.
Results:
Xenon exposure was found to decrease the in vitro enzymatic activity of recombinant human furin by 96-99%. Fluorescence measurements were taken for 24 hours and the enzyme inhibition persisted for the duration of the experiment. Further studies will be necessary to better characterize the exact duration of this inhibition.
Conclusions:
These findings appear to be the first to report xenon as a furin inhibitor. The observed inhibition continued throughout the duration of the experiment. The effectiveness of xenon as a furin inhibitor, its favorable side effect profile, and its long history of safe use as an anesthetic, when used under direct medical supervision, make it a promising treatment for diseases facilitated by furin or its substrates. Further studies in cell culture or clinical trials may expand its clinical role for such diseases.
Aims:
Certain cancers, pathogenic infections, and other diseases are facilitated by the host enzyme furin, a calcium-dependent serine protease that is the most prominent member of the family of proprotein convertases. Furin and the other proprotein convertases modify certain other proteins to change them from their inactive to active forms. Previous attempts to find an effective, non-toxic furin inhibitor to treat diseases facilitated by furin have had only limited success, due to toxicity or large molecular size that impedes absorption of the molecule. This has placed increased importance on the development of small-molecule furin inhibitors. The object of this study was to consider the effect of the noble gas xenon as a furin inhibitor.
Methods:
This study uses a fluorometric furin inhibition assay to compare the enzymatic activity of recombinant human furin after exposure to 99.999% xenon gas, compared to the enzymatic activity of untreated recombinant human furin.
Results:
Xenon exposure was found to decrease the in vitro enzymatic activity of recombinant human furin by 96-99%. Fluorescence measurements were taken for 24 hours and the enzyme inhibition persisted for the duration of the experiment. Further studies will be necessary to better characterize the exact duration of this inhibition.
Conclusions:
These findings appear to be the first to report xenon as a furin inhibitor. The observed inhibition continued throughout the duration of the experiment. The effectiveness of xenon as a furin inhibitor, its favorable side effect profile, and its long history of safe use as an anesthetic, when used under direct medical supervision, make it a promising treatment for diseases facilitated by furin or its substrates. Further studies in cell culture or clinical trials may expand its clinical role for such diseases.
