A novel strategy to generate biologically active neo-glycosaminoglycan conjugates

Glycobiology. 1999 Dec;9(12):1331-6. doi: 10.1093/glycob/9.12.1331.

Abstract

Heparin and heparan sulfate are structurally related polysaccharides with a variety of biological effects/functions. Most of these effects are due to interactions, of varying specificity, between the negatively charged polysaccharide chains and proteins. While such interactions generally involve a single saccharide domain of decasaccharide size or less, ternary complexes of two protein molecules binding to separate domains on a single polysaccharide chain are known to occur. To facilitate studies on domain organization and its importance for biological function a strategy was developed to chemically conjugate defined heparin oligomers in linear and chemoselective fashion. The procedure requires that the oligosaccharide to provide the reducing-terminal domain of the conjugate is generated by lyase degradation of a parent polysaccharide, whereas the nonreducing-terminal domain is obtained through deaminative cleavage with nitrous acid. The applicability of the method was demonstrated by constructing a conjugate composed of two heparin 12-mers, of which the reducing-terminal component contained the antithrombin-binding region, whereas the nonreducing-terminal domain did not. Contrary to any of the unconjugated oligomers, the product was found to efficiently promote the inactivation of thrombin by antithrombin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / pharmacology
  • Antithrombins / chemistry
  • Antithrombins / pharmacology
  • Chromatography, Gel
  • Glycosaminoglycans / chemistry*
  • Glycosaminoglycans / pharmacology
  • Heparin / chemistry*
  • Heparin / pharmacology
  • Molecular Structure
  • Oligosaccharides / chemistry
  • Osmolar Concentration
  • Thrombin / antagonists & inhibitors

Substances

  • Anticoagulants
  • Antithrombins
  • Glycosaminoglycans
  • Oligosaccharides
  • Heparin
  • Thrombin