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Correlation between structure and function of heparin.

R D Rosenberg, L Lam

    Proceedings of the National Academy of Sciences of the United States of America
    |March 1, 1979
    PubMed
    Summary
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    Highly active heparin contains a specific tetrasaccharide sequence responsible for its anticoagulant properties. This unique structure, identified through nitrous acid degradation, is crucial for heparin

    Area of Science:

    • Biochemistry
    • Pharmacology
    • Molecular Biology

    Background:

    • Heparin is a complex polysaccharide with significant anticoagulant activity.
    • Variations in heparin structure influence its biological potency.
    • Identifying the specific structural motifs responsible for heparin's activity is crucial for understanding its mechanism.

    Purpose of the Study:

    • To fractionate crude porcine heparin and isolate species with varying anticoagulant activities.
    • To characterize the specific tetrasaccharide structure present in highly active heparin.
    • To correlate the abundance of this tetrasaccharide with heparin's anticoagulant potency.

    Main Methods:

    • Fractionation of crude porcine heparin based on molecular weight and activity.
    • Nitrous acid degradation to yield tetrasaccharide fragments.

    Related Experiment Videos

  • Structural analysis of tetrasaccharide fractions using chemical and analytical methods.
  • Quantification of specific tetrasaccharide structures in active and inactive heparin species.

    • Main Results:

    • Two heparin fractions with distinct anticoagulant activities (360 and 12 units/mg) were obtained.
    • A unique tetrasaccharide (1betaa) was isolated from highly active heparin, comprising L-iduronic acid → N-acetylated D-glucosamine-6-sulfate → D-glucuronic acid → N-sulfate D-glucosamine-6-sulfate.
    • This specific tetrasaccharide sequence was found in 95% of the 1betaa fraction derived from highly active heparin.
    • Relatively inactive heparin yielded a heterogeneous tetrasaccharide mixture (1betai), with only 8.5% sharing the 1betaa structure.

    Conclusions:

    • The unique tetrasaccharide sequence (1betaa) is highly abundant in potent anticoagulant heparin.
    • A small percentage (2.6%) of inactive heparin molecules contain this critical sequence.
    • The identified tetrasaccharide structure is strongly correlated with heparin's anticoagulant activity and likely represents the key functional site.