Synthetic inhibitors of human leukocyte elastase Part 1--Sulphated polysaccharides.
Ten dextran sulphates and six chitosan sulphates of variable Mr and extent of sulphate substitution have been examined for their ability to inhibit human leukocyte elastase (HLE). All were potent partial non-competitive inhibitors of this enzyme, highest activity being obtained with compounds of large molecular weight and maximum sulphate incorporation (Ki = 5.0 X 10(-10)M]. In all cases, the dextran sulphates were more effective inhibitors than chitosan sulphates of similar size and charge, but both classes were inactive against bovine trypsin, chymotrypsin and porcine pancreatic elastase at concentrations less than 10(-4)M. The data suggest that drug binding to HLE occurs by stereospecific electrostatic interactions at site(s) removed from the catalytic reaction centre.
Lentini
A
A
Ternai
B
B
Ghosh
P
P
D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048271:Chitosan; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000097:blood*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013464:Sulfuric Acids / Q000494:pharmacology
D003911:Dextrans; D013464:Sulfuric Acids; D002686:Chitin; D048271:Chitosan; D016264:Dextran Sulfate; D010196:Pancreatic Elastase