Abstract
SummaryThe glycosaminoglycan, heparan sulfate (HS) is composed of alternating units of hexuronic acid and glucosamine, that are variously sulfate-substituted at different positions. Proteoglycans carrying HS chains are ubiquitously expressed at cell surfaces and in the extracellular matrix. The structures of these chains are highly variable, yet under strict bio-synthetic control. Due to their high negative charge,HS chains interact with a multitude of proteins, including growth factors/morphogens and their receptors, chemokines, and extracellular-matrix proteins.These interactions regulate key events in embryonic development and in homeostasis. HS-protein interactions vary with regard to specificity, and often seem to depend primarily on charge density rather than on strict carbohydrate sequence.The organization of sulfated domains along the HS chain appears to be of importance. HS-protein interactions are involved in a variety of pathophysiological processes, including inflammation, angiogenesis, and amyloid deposition. Drugs targeting such interactions may be useful in treatment of disease conditions as diverse as cancer, inflammatory bowel disease, and Alzheimer’s disease. Potential drugs may mimick HS oligosaccharides, but could also be peptides blocking the protein-binding domains of HS chains. Drug generation requires a firm understanding of the pathophysiological role of a given HS-protein interaction, and of the aspect of specificity.Even inhibition of HS biosynthesis may be considered.
Funder
Swedish Research Council
Swedish Cancer Society
Swedish Foundation for Strategic Research
Polysackaridforskning AB
Cited by
101 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献