Single‐Step Per‐O‐Sulfonation of Sugar Oligomers with Concomitant 1,6‐Anhydro Bridge Formation for Binding Fibroblast Growth Factors

• Published in: Chembiochem : a European journal of chemical biology 2019-01, Vol.20 (2), p.237-240
• Main Authors: Yeh, Che‐Jui, Ku, Chiao‐Chu, Lin, Wei‐Chen, Fan, Chiao‐Yuan, Zulueta, Medel Manuel L., Manabe, Yoshiyuki, Fukase, Koichi, Li, Yaw‐Kuen, Hung, Shang‐Cheng
• Format: Article
• Language: English
• Subjects: anhydrosugars; Binding; Cancer; carbohydrates; Cell surface; Dimethylformamide; Disaccharides; Embryos; fibroblast growth factors; Fibroblasts; Glycosaminoglycans; Growth factors; Heparan sulfate; Oligomers; oligosaccharides; per-O-sulfonation; Proteins; Reagents; Sugar; Sulfates; Sulfonation; Sulfur trioxide; synthetic methods
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201800464

Many circulating cancer‐related proteins, such as fibroblast growth factors (FGFs), associate with glycosaminoglycans—particularly heparan sulfate—at the cell surface. Disaccharide analogues of heparan sulfate had previously been identified as the shortest components out of the sugars that bind to FGF‐1 and FGF‐2. Taking note of the typical pose of l‐iduronic acid, we conceived of per‐O‐sulfonated analogues of such disaccharides, and devised a single‐step procedure for per‐O‐sulfonation of unprotected sugars with concomitant 1,6‐anhydro bridge formation to achieve such compounds through direct use of SO3⋅Et3N as sulfonation reagent and dimethylformamide as solvent. The synthesized sugars based on the oligomaltose backbone bound FGF‐1 and FGF‐2 mostly at the sub‐micromolar level, although the tetrasaccharide analogue achieved low‐nanomolar binding with FGF‐2. Sugar sulfonation: A single‐step process for per‐O‐sulfonation of unprotected sugars with concomitant 1,6‐anhydro bridge formation, affording analogues of previously identified heparan sulfate disaccharides that associate with FGF‐1 and FGF‐2, has been developed. The synthesized sugars bound FGF‐1 and FGF‐2 mostly at the sub‐micromolar level, but the tetrasaccharide achieved low‐nanomolar binding with FGF‐2.