Dextran sulphate—a synthetic analogue of heparin

Abstract

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

Dextran Sodium Sulfate-Induced Colitis in Germ-Free IQI/Jic Mice.

“…We did not observe any mucosal destruction in the intestines of these mice and therefore concluded that this was not the cause of the bleeding into the large intestine of GF mice. The mechanism by which massive blood loss into the intestinal lumen is occurred was not clear, however, DSS is an analog of heparin and it has anticoagulant activity [11,24], its action on the clotting cascade may 4. Histopathological findings of the large intestine of GF and CVz mice on day three after administration of 5% DSS.…”

“…Dextran, which has the same structure as DSS except without the sulfate ester, is hydrolyzed into small fragments by incubation with rat cecal contents [16]. DSS is composed of α-1, 6-linked D-glucose and contains up to three sulfate esters per sugar unit [24] which reportedly stabilize glycosidic linkages [23].…”

Histamine Release in Rabbit Blood by Dextran and Dextran Sulphate

“…samples of dilute plasma were submitted to the extraction procedure described by McIntire, Roth, and Shaw (1947) (Boura, Mongar, and Schild, 1954;Schild, 1947) by the 2 x 2 assay technique (Schild, 1942) Details of the polysaccharides used in these experiments were supplied by Dr. C. R. Ricketts and are given in Table I. Most of the data and the methods used to determine the intrinsic viscosities and molecular weights of the compounds have been published (Ricketts, 1952a(Ricketts, , 1952bRicketts and Walton, 1952;Walton, 1952). The dextran of intrinsic viscosity 0.02 did no cause a significant rise in the plasma histamir levels above those of the control samples, but iL creases obtained with those fractions having i] trinsic viscosities ranging from 0.12 to 0.64 we significant at the P. 0.05 level (Table II).…”

“…These results suggested that sulphation of the dextran was necessary in order to obtain compounds capable of inhibiting the histamine release reaction, and it seemed possible that sulphation of other polysaccharides would give rise to the same properties. Recent work (Ricketts, 1952a) showed that sulphuric esters of polysaccharides of low molecular weight possessed anticoagulant activity in vitro. The effect of one of these, maltotriose sulphate, was compared with that of heparin in its ability to inhibit the histamine-releasing action of dextran sulphate D/3 in rabbit blood.…”

“…No attempts were made to confirm this, since by analogy with the anticoagulant action of dextran sulphate (Ricketts, 1952b) it was thought that the degree to which a particular fraction had been sulphated might also prove to be an additional factor in modifying activity. Those samples which were available at the time had not been sulphated to the same extent.…”