Potent selective nonpeptidic inhibitors of human lung tryptase
AUTOR(ES)
Burgess, Laurence E.
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17520Documentos Relacionados
- (4-Aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase
- Design of potent and selective human cathepsin K inhibitors that span the active site
- Identification of highly potent and selective inhibitors of Toxoplasma gondii dihydrofolate reductase.
- Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
- Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation.