Heparin, the drug of choice for the prevention and treatment of thromboembolic disorders, has been shown to interact with many proteins. Despite its widespread medical use, little is known about the precise sequences that interact with specific proteins. The minimum heparin binding sequence for FGF1 and FGF2 necessary to promote signaling was investigated. A characteristic pentasaccharide sequence, DEFGH, is required to accelerate the inhibition of thrombin and factor Xa in the blood-coagulation cascade. The first synthetic heparin pentasaccharide drug has been approved in Europe and the US and is sold under the trade name Arixtra. Other oligosaccharides with different composition are under clinical investigation. The enormous interest in the assembly of heparin oligosaccharides will stimulate the development of new synthetic approaches. Heparin-oligosaccharide-synthesis automation similar to that of DNA or peptide synthesis will play an important role.
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