Synthesis, Conformational Analysis and Comparative Protein Binding of a Galabioside and Its Thioglycoside Analogues

The two thio analogues ( 2 and 3 ) of TMSEt galabioside [2‐(trimethylsilyl)ethyl 4 ‐ O ‐(α‐D‐galactopyranosyl)‐β‐D‐galactopyranoside, 1 ], having anomeric sulfur instead of anomeric oxygen atoms, were synthesized and their conformations investigated by NMR and computational (MM 3) methods. A spacer galabioside was covalently coupled to aminated microtiter plates, and binding of a bacterial pilus adhesin (PapG) to the plates was inhibited by the soluble ligands 1, 2 and 3 . The ligand 2 , which has an intersaccharidic sulfur linkage, was a much less efficient inhibitor than 1 , which has the natural oxygen linkage. The inhibitory power of ligand 3 was only slightly less than that of 1 . An NMR experiment with 1 and 2 , in which hydroxyl‐group hydrogens had been partially (50%) substituted by deuterium, demonstrated the presence (in 1 ) and absence (in 2 ) of an intramolecular (HO 2′ – HO 6) hydrogen bond. This result indicates that the conformations of 1 and 2 are different and that the difference is sufficient to cause the observed (≈ 30 times) reduction of the saccharide‐protein binding strength.