Mechanism-based inhibitors of serine proteinases based on the Gabriel-Colman rearrangement.
Neutrophil-derived mediators such as, for example, the serine proteinase elastase, cathepsin G and proteinase 3, play a critical role in inflammatory lung disease. This report describes the design, synthesis and in vitro inhibitory activity of some novel mechanism-based inhibitors of human leukocyte elastase and cathepsin G. The design of the inhibitors is based on the Gabriel-Colman rearrangement. The behavior of the synthesized compounds toward elastase and cathepsin G with respect to inhibitory prowess, mode of interaction, specificity, etc., has been found to be dependent on the recognition and reactivity elements present in each inhibitor.
Groutas
W C
WC
Department of Chemistry, Wichita State University, Kansas 67208.
Chong
L S
LS
Venkataraman
R
R
Epp
J B
JB
Kuang
R Z
RZ
Brubaker
M J
MJ
Houser-Archield
N
N
Huang
H
H
McClenahan
J J
JJ
D000595:Amino Acid Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases
D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase