In silico design of halogenated carbohydrate mimetics as potential halogen-bonding ligands

1749-016 Lisboa, Portugal Abstract The molecular recognition of carbohydrates by proteins is characterized by the presence of classical hydrogen bonds stabilizing binding together with an important contribution from other intermolecular interactions conferring high specificity. [1] The design of glycomimetic ligands as modulators of protein-carbohydrate binding events is a common approach in the context of chemical glycobiology [2] and carbohydrate-based drug discovery. [3] While a diversity of functional groups has been successfully introduced in carbohydrate structures, [2] the use of halogens has been largely neglected, except for fluorine. However, heavier halogens (X = Cl, Br, or I) can establish highly directional, R–X ××× B interactions with Lewis bases (B), known as halogen bonds (HaB). These interactions have been mostly explained by the presence of an electropositive site at the outermost region of X species, named sigma-hole. [4] HaB-mediated molecular recognition phenomena are widespread across biological systems and have been used as tools in medicinal chemistry, [5]