Potent selective nonpeptidic inhibitors of human lung tryptase.
نویسندگان
چکیده
Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure-activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented.
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عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 96 15 شماره
صفحات -
تاریخ انتشار 1999