| Affiliation: | 1. Genomics Research Center, Academia Sinica No. 128, Section 2, Academia Road, Taipei, 115 Taiwan
Department of Applied Chemistry, National Chiao Tung University, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan;2. Genomics Research Center, Academia Sinica No. 128, Section 2, Academia Road, Taipei, 115 Taiwan;3. Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 560-0043 Japan;4. Department of Applied Chemistry, National Chiao Tung University, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan |
| Abstract: | 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. |
