| Keratan sulfate (KS)-a linear, unbranched, sulfated polysaccharide consisting in part of repeating beta-1,4-linked galactose (Gal) and 2-acetamido-2-deoxy-D-glucopyranose (GlcNAc) groups -is considered the most diverse of all glycosaminoglycans (GAGs). Despite its immense biological importance, KS has attracted almost no attention from the synthetic community. In the last decade, enzymes responsible for the biosynthesis of KS were identified and some progresses were made in the enzymatic synthesis of the KS fragments. However, these enzymatic syntheses also produced very complex and heterogeneous mixtures of polysaccharides. Thus, it is indispensable to access structurally pure and well-defined KS fragments to understand their recognition and activities towards different proteins, which will eventually lead to the development of new therapeutics for KS-related diseases. Herein I present an efficient and robust synthetic strategy for the iterative solution-phase synthesis of the highly sulfated repeating KSI disaccharide unit using a fluorous tag amenable to automated solution-phase synthesis. This approach allows diversification at the non-reducing end as well as flexibility in the sulfation patterns to facilitate the combinatorial synthesis of a range of KS fragments. |
