Requirement of free carboxyl groups for the anticoagulant activity of heparin.
The uronic acid carboxyl groups of a heparin fraction with high anticoagulant activity, were converted to the methyl ester by treatment with diazomethane. The product obtained after purification did not have the characteristic activity of heparin in accelerating the inhibition of thrombin or factor Xa, by antithrombin. Esterification also abolished the binding of heparin to antithrombin as measured by changes in the intrinsic fluorescence. It is concluded that free carboxyl groups are essential for the activity of heparin.
D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000378:metabolism; D002245:Carbon Dioxide / Q000502:physiology*; D003864:Depression, Chemical; D003978:Diazomethane / Q000494:pharmacology; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006493:Heparin / Q000502:physiology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D000991:Antithrombins; D002245:Carbon Dioxide; C041069:carboxyl radical; D003978:Diazomethane; D005170:Factor X; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa