Structure of the Antithrombin III-Binding site in Heparin
1979; Thieme Medical Publishers (Germany); Linguagem: Inglês
10.1055/s-0039-1684700
ISSN2567-689X
AutoresUlf Lindahl, G. Bäckström, N. Höök, Johan Riesenfeld, L Thunberg, L A Fransson, Alfred Linker,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoFragments with high affinity for antithrombin III (AT), composed of 12 to 16 monosaccharide units, were isolated from heparin after partial chemical or enzymatic depolymerization of the polysaccharide. Analysis of such fragments based on identification ot deamination products suggested that nonsulfated L-iduronic acid (a minor constituent) is essential for the anticoagulant activity of heparin. The location of this unit in the AT-binding sequence was determined by periodate oxidation. Furthermore, an N-sulfate group essential for activity was located by structural analysis of partially N-desulfated fragments retaining high affinity for AT. It is proposed that the AT-hinding sequence in heparin has a variable structure containing certain nonvanable regions. A tentative structure for this sequence is presented, with indication of identified constant and variable regions. (Supported by grant No. 2309 from the Swedish Medical Research Council).
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