Fluorous tags for the synthesis of heparan sulfate libraries using a split-mix final demixing strategy

摘要

Glycosaminoglycans, a class of linear polysaccharides composed of repeating lisaccharide units containing a hexosamine and an uronic acid, are important polysaccharides bund in many tissues. They participate in many biological processes through the regulation of various proteins, including growth factors, chemokines, cytokines, cell adhesion molecules... The 2O_(10) glycoconjugate (formed by two octasaccharides bound by a spacer of 50 A) showed a good affinity for interferon-γ (IFNγ) and has the capacity to inhibit the cytokine pro-inflammatory activity. In order to optimize the affinity and selectivity of 20 for IFNy, the development of focused combinatorial library of heparan sulfate (HS) octasaccharides would be of great interest. We have recently shown that split-mix synthesis followed by charge based demixing is an efficient strategy for the synthesis of HS tetrasaccharide libraries.3 Although charge based demixing by chromatography on RP-C18 is highly efficient, it requires different charge state for the library members.