Synthesis and biological evaluation of a unique heparin mimetic hexasaccharide for structure-activity relationship studies

J Med Chem. 2014 Jun 12;57(11):4511-20. doi: 10.1021/jm4016069. Epub 2014 May 19.


To date, the structure-activity relationship studies of heparin/heparan sulfate with their diverse binding partners such as growth factors, cytokines, chemokines, and extracellular matrix proteins have been limited yet provide early insight that specific sequences contribute to this manifold biological role. This has led to an impetus for the chemical synthesis of oligosaccharide fragments of these complex polysaccharides, which can provide an effective tool for this goal. The synthesis of three heparin mimetic hexasaccharides with distinct structural patterns is described herein, and the influence of the targeted substitution on their bioactivity profiles is studied using in vitro affinity and/or inhibition toward different growth factors and proteins. Additionally, the particularly challenging synthesis of an irregular hexasaccharide is reported, which, interestingly, in spite of being considerably structurally similar with its two counterparts, displayed a unique and remarkably distinct profile in the test assays.

MeSH terms

  • Cytokines / chemistry
  • Glucuronidase / antagonists & inhibitors
  • Heparin / chemistry*
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Molecular Mimicry
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / chemistry
  • Protein Binding
  • Structure-Activity Relationship
  • Sulfonic Acids / chemical synthesis
  • Sulfonic Acids / chemistry


  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Oligosaccharides
  • Sulfonic Acids
  • Heparin
  • heparanase
  • Glucuronidase