Celsus Laboratories

HEPARAN SULFATES

HEPARAN SULFATE [HS-0301], otherwise known as heparitin sulfate or heparin monosulfate, is a generic term describing polysaccharides which are linear and consist of N-acetylated [→4)∝-D-GlcNpAc-(1→4)β-D-GlcAp(1→] and N-sulfated disaccharides [→4)∝-D-GlcNpS-(1→4) -β-D-GlcAp or ∝-L-IdoAp(1→] that are arranged mainly in a segregated manner. Approximately 25% of the total polymer is initially formed by alternating arrangements of the two disaccharide units, →4)α-D-GlcNpS (1→4)UAp(1→4)α-D-GlcNpAc(1→4)UAp (1→4)α-D-GlcAp(1→. The polymer is formed as a repeating →4)α-D-GlcNpAc(1→4)β-D-GlcAp(1→ disaccharide sequence that is attached to a serine residue of a core protein through a tetrasaccharide, glucuronosyl→galactosyl→ galactosyl→xylosyl, linkage region. It then undergoes partial Ndeacetylation followed by N-sulfation of the newly exposed amino groups, partial C-5 epimerization of D-GlcAp to L-IdoAp and O-sulfation. O-sulfates are always found in proximity to N-sulfates which enhances the clustering of the sulfate residues and the heterogeneity in chemical composition and charge density of heparan sulfate.

HEPARAN FRACTION I I [HO-0310] comprises primarily ΔUA→GlcNAc (≈ 75%) and is resistant to degradation by heparin lyase I, consistent with its being a heparan sulfate. The sulfate-rich fractions in heparan sulfate are more heparin-like, though they rarely possess the sulfate density found in heparin.

References

Griffin CC, Linhardt RJ, Van Gorp CL, Toida T, Hileman RE, Schubert RL, Brown SE. Isolation and characterization of heparan sulfate from crude porcine intestinal mucosa peptidoglycan. Carbohydr Res 1995; 276:183-197.
Linhardt RJ, Hileman RE, Griffin CC, Brown SE, Schubert RL, Van Gorp CL. Characterization of a heparan sulfate fraction (CL-03105). Thromb Haemost 1995; 73(6):1352.
Crutcher KA, Harmony JA. Methods for the treatment of apolipoprotein E related diseases. PCT WO 98/01101 (1997).
Schwartz D, Yang L, Ghigliotti G, Griffin C, Van Gorp C, Abenschein D, Eisenberg P. Efficacy of heparan sulfate in inhibiting vascular wall procoagulant activity after arterial injury and neointimal thickening. AHA, submitted.


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