Inhibition of human leukocyte elastase by chemically and naturally oversulfated galactosaminoglycans.
Several samples of oversulfated chondroitin and dermatan were obtained by chemical sulfation and by SAX-HPLC enrichment. The starting products and oversulfated products were tested as potential inhibitors of human leukocyte elastase, an enzyme hypothesized to be involved in the etiology of diseases such as emphysema, atherosclerosis, and rheumatoid arthritis. Chemical oversulfation (SO3H/COOH 1.6-3.2), preferentially occurring at C-6 of galactosamine residues, was found generally to increase the inhibitory power on elastase. Chemically oversulfated galactosaminoglycans thus have potential as therapeutic agents, considering that they produce non-significant effects on the hemocoagulative system. Two naturally oversulfated dermatans sulfate (SO3H/COOH ca. 1.2), mainly oversulfated at C-2 of iduronic acid residues, showed comparatively higher anticoagulant activity (in the HC-II mediated thrombin inhibition test).
Istituto di Strutturistica Chimica G. Giacomello, CNR, Rome, Italy.
C
C
Bartolucci
L
L
Cellai
M A
MA
Iannelli
D
D
Lamba
L
L
Liverani
G
G
Mascellani
E
E
Perola
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002240:Carbohydrate Sequence; D002356:Cartilage / Q000737:chemistry; D002417:Cattle; D002809:Chondroitin Sulfates / Q000378:metabolism / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D012754:Sharks; D013431:Sulfates / Q000378:metabolism; D013461:Sulfur Oxides / Q000378:metabolism
D004791:Enzyme Inhibitors; D011134:Polysaccharides; D013431:Sulfates; D013461:Sulfur Oxides; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates; C007815:galactosaminoglycan; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; C011118:sulfur trioxide