Dextran sulphate--a synthetic analogue of heparin.

The structure of the natural anticoagulant, heparin, is gradually being elucidated. As each step forward is made, attempts to synthesize molecules with the biological activity of heparin receive renewed impetus. It is now known (Jorpes, 1939) that heparin is composed of glucuronic acid and glucosamine though the mode of linkage of these two parts is not yet clear. Some of the hydroxyl groups of these components are esterifiedwith sulphuric acidbut the exact distribution of sulphate groups is uncertain. Recently, however, Jorpes, Bostrom & Mutt (1950) have shown that during the weak acid hydrolysis of heparin, sulphuric acid appears at the same time and with the same rate as amino groups, leading to the view that the amino group is combined with sulphuric acid. This conclusion is confirmed by the work of Meyer & Schwartz (1950). An important contribution to our knowledge of the size of heparin molecules wasmade by Gronwall, Ingleman & Mosiman (1945), who measured sedimentation anddiffusion constants fora substantially purepreparationintheultracentrifuge. Sinceheparin is not absolutely homogeneous as regards molecular size it was not possible to calculate an exact value but a molecular weight of 17 000 was obtained as an average for all the molecules in the preparation. Heparin is also inhomogeneous in respects other than molecular weight. Several mild physical methods have been employed to divide seemingly pure samples ofheparin into components differing in sulphur and nitrogen content and activity. Fractional recrystallization of the brucine salt by Jorpes & Bergstrom (1937) pointed to the association of sulphur content with activity. In the Craig countercurrent extractor O'Keef, Russo-Alesi, Dolliver & Stiller (1949) separated heparin into a component having 8-2 % S and an activity of 59 units/mg. and one with 13 3 % S and an activity of 215 units/mg. By the technique of frontal analysis, Jensen, Sneilman & Sylven (1948) detected three or four components in heparin. From the facts outlined above, it appears that blood anticoagulant activity is not the property of a unique molecular configuration but is shared by a number of similar molecules occurring in the product ordinarily called heparin. An outstanding feature which has long been recognized is the neces-