Heparin is a strongly sulfated glycosaminoglycan containing alternating glucosamine-derived and uronic acid residues, including iduronic acid and glucuronic acid. Chains vary in length and chemical substitution, so a preparation is not adequately described by one small-molecule molecular formula. Sulfation and carboxylate groups contribute substantial negative electric charge.[ref]
Heparin lyase in IUBMB Enzyme Nomenclature. EC 4.2.2.7: uronate and sulfated glucosamine-containing polysaccharide substrate
A defined fragment can test which structural details matter. In 1983, J. Choay and collaborators synthesized related four- and five-sugar fragments and verified their structures with nuclear magnetic resonance. The five-sugar fragment bound antithrombin and enhanced its inhibition of factor Xa, while the tested four-sugar fragment did not.[ref]
Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity by J. Choay and others. Abstract: structural verification, antithrombin binding and anti-factor Xa activity
The experiment shows why counting sulfate groups or measuring total charge cannot by itself specify biological activity: a particular arrangement of residues also matters. This is a molecular structure–function example, distinct from selecting a clinical dose or predicting every property of an unfractionated preparation.
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