Heparin (H) and heparan sulfate (HS) are linear polysaccharides composed of alternating units of variously sulfated D-glucosamine (GlcN) and L-iduronic (IdoA) or D-glucuronic (GlcA) acid units. These structurally related glycosaminoglycans interact with a large number of proteins of diverse biological functions.
Heparin–protein interactions modulate the biological activities of numerous proteins, such as growth factors, cytokines, viral proteins, and coagulation factors. It is commonly assumed that specific oligosaccharide structures might be responsible for the binding to individual proteins. Therefore, structurally defined H/HS sequences are necessary for the precise elucidation of the mode of H/HS actions on their target molecules. Obtaining homogeneous oligosaccharides of well-defined structures from the natural polysaccharides is extremely difficult due to their inherent heterogeneity in terms of sequence and sulfation pattern. Chemical synthesis, on the other hand, is able to provide specific H/HS oligosaccharides.
In a project on the antitumor effects of H/HS, a series of differently sulfated hexasaccharides (1, 2, 3) were needed in relation to the overexpression/silencing of specific sulfotransferase enzymes. Previously, we have reported [1] the synthesis of structurally related tetrasaccharides from a single orthogonally protected precursor. Herein we report the extension of the orthogonal protection strategy to hexasaccharides. All the sulfated oligosaccharides are prepared from a common, orthogonally protected derivative (4) having (1-naphtyl)methyl, (4-methoxy)phenyl and benzoyl as orthogonal protecting groups.
Acknowledgement: This work is supported by ERA Chemistry (Grant OTKA 85216) and National Development Agency (Grant K-TÉT_10-1-2011-0053).
References:
[1] Jakab Zs; Fügedi P, 26th International Carbohydrate Symposium, Madrid, Spain, July 22-27, 2012. Abstract P072.
