Heparin is a natural polysaccharide that contains a large number of linear and polydisperse chains. Molecular weight of natural heparin ranges from 3.000 to 30.000 Daltons (Da), while medical grade
unfractioned heparin has an average molecular weight of 12 to 16.000 Da.
Heparin chains are compose of long fully sulfated segments interrupted with undersulfated domains. Composition in terms of disaccharidic sequences is considerably heterogeneous. The mayor repeating unit is the trisulfated disaccharide 2-O-sulfo-α-L-iduronic acid 1"4 linked to 6-O-sulfo-N-sulfo-α-D-glucosamine ("4]IdoA2S(1"4)GlcNS6S[1") whereas different minor disaccharides comprise the variable sequences (See Fig. 1A and 1B).
Only a third of the chains in the pharmaceutical-grade heparin contains the pentasaccharide GlcNAc/NS6S → GlcA → GlcNS3S,6S → IdoA2S → GlcNS6S with a 3-O-sulphated residue at its central position. This sequence constitutes the ATIII binding site, essential for heparinís anticoagulant activity. (See Fig. 2).
Figure. Heparinís Antithrombin III binding site and its structural variants.