Effect of oversulfation on the chemical and biological properties of chondroitin-4-sulfate.
Chondroitin-4-sulfate was oversulfated using chlorosulfonic acid-pyridine complex and was isolated as the sodium salt. A comparison of the infrared analysis of the native (N-2) and oversulfated (S-2) compounds showed that the two spectra were identical except for a new peak in S-2 at 825 cm corresponding to the equatorial C-6 position of galactosamine. There was a 2.7-fold increase of sulfate content in S-2 and a generation of a significant anticoagulant activity as measured by doubling of the prothrombin time of normal citrated human plasma using 7.5 microg, while N-2 was inactive even at 2,000 microg. The result of the in-vitro studies of the activation of glutamic plasminogen by tissue plasminogen activator (t-PA) or by high-molecular-weight urokinase using 0.05 mol/l Tris buffer (pH 7.35) containing a physiological concentration of NaCl (0.9%) showed that 28.6 microg/ml S-2 enhanced the activation by three-fold to four-fold by t-PA or by urokinase, while the same concentrations of N-2 or unfractionated heparin gave less than 30% enhancement of t-PA and no enhancement of urokinase. The mechanism of enhancement by S-2 was investigated by dilution studies. The results showed that S-2 interacted with both urokinase or t-PA and glutamic plasminogen favoring a template model, while N-2 or unfractionated heparin interacted only with t-PA.
Carranza
Yaneth E
YE
Department of Chemistry at Prairie View A&M University, Prairie View, Texas 77445, USA.
Durand-Rougley
Clarissa
C
Doctor
Vasant
V
D001777:Blood Coagulation / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000737:chemistry*; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005341:Fibrinolysin / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010949:Plasma; D010958:Plasminogen / Q000187:drug effects / Q000378:metabolism; D011517:Prothrombin Time; D011725:Pyridines / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013431:Sulfates / Q000032:analysis*; D013451:Sulfonic Acids / Q000494:pharmacology; D013925:Thromboplastin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D011725:Pyridines; D013431:Sulfates; D013451:Sulfonic Acids; C013880:chlorosulfonic acid; D010958:Plasminogen; D006493:Heparin; D002809:Chondroitin Sulfates; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; C023666:pyridine