Biotechnological engineering of heparin/heparan sulphate: a novel area of multi-target drug discovery

Curr Pharm Des. 2005;11(19):2489-99. doi: 10.2174/1381612054367553.


Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticoagulants / therapeutic use
  • Bacterial Capsules
  • Heparin / biosynthesis*
  • Heparin / therapeutic use
  • Heparitin Sulfate / biosynthesis*
  • Heparitin Sulfate / therapeutic use
  • Humans
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Polysaccharides, Bacterial / biosynthesis
  • Polysaccharides, Bacterial / therapeutic use
  • Technology, Pharmaceutical / methods*
  • Technology, Pharmaceutical / trends
  • Venous Thrombosis / etiology
  • Venous Thrombosis / prevention & control


  • Anticoagulants
  • Polysaccharides, Bacterial
  • capsular polysaccharide K5
  • Heparin
  • Heparitin Sulfate