Active site mapping of the serine proteases human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II, bovine chymotrypsin A.alpha., and Staphylococcus aureus protease V-8 using tripeptide thiobenzyl ester substrates

Biochemistry ◽  
1984 ◽  
Vol 23 (13) ◽  
pp. 2995-3002 ◽  
Author(s):  
J. Wade Harper ◽  
Robert R. Cook ◽  
C. Justine Roberts ◽  
Beth H. McLaughlin ◽  
James C. Powers
Keyword(s):  
Active Site ◽  
Serine Proteases ◽  
Human Leukocyte ◽  
Cathepsin G ◽  
Leukocyte Elastase ◽  
Pancreatic Elastase ◽  
Site Mapping ◽  
Human Leukocyte Elastase ◽  
Porcine Pancreatic Elastase ◽  
And Staphylococcus Aureus

Synthesis of 2-Phenylisothiazol-3(2H)-One 1,1-Dioxides: Inhibitors of Human Leukocyte Elastase

2003 ◽  
Vol 58 (1) ◽  
pp. 111-120 ◽  
Author(s):  
Michael Gütschow ◽  
Markus Pietsch ◽  
Kathleen Taubert ◽  
Tonia H. E. Freysoldt ◽  
Bärbel Schulze
Keyword(s):  
Active Site ◽  
Serine Proteases ◽  
Human Leukocyte ◽  
Cathepsin G ◽  
Time Dependent ◽  
Dependent Manner ◽  
Complex Type ◽  
Leukocyte Elastase ◽  
Human Leukocyte Elastase ◽  
Kinetic Investigations

Abstract A series of 2-phenylisothiazol-3(2H)-one 1,1-dioxides 14a - q were synthesized by oxidation of isothiazolium perchlorates 12. The inhibition of the serine proteases cathepsin G, chymotrypsin and human leukocyte elastase (HLE) by 14 was investigated. Some 4,5-diphenyl substituted derivatives ( 14i - k) were found to inhibit HLE in a time-dependent manner and exhibited kobs/[I] values > 500 M−1s−1. 14k (kobs/[I] = 2400 M−1s−1), was the most potent HLE inhibitor of this series. Kinetic investigations led to the conclusion that 2-phenylisothiazol-3(2H)-one 1,1-dioxides interact with HLE at the active site as well as at another binding site, resulting in a complex type of inhibition.

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