Detalle de: Conformational Selection in Glycomimetics: Human Galectin‐1 Only Recognizes syn ‐ Ψ ‐Type Conformations of β‐1,3‐Linked Lactose and Its C ‐Glycosyl Derivative

The human lectin galectin‐1 (hGal‐1) translates sugar signals, that is, β‐galactosides, into effects on the level of cells, for example, growth regulation, and has become a model for studying binding of biopharmaceutically relevant derivatives. Bound‐state conformations of Galβ‐ C ‐(1→3)‐Glcβ‐ O Me ( 1 ) and its βGal‐(1→3)‐βGlc‐OMe disaccharide parent compound were studied by using NMR spectroscopy (transferred (TR)‐NOESY data), assisted by docking experiments and molecular dynamics (MD) simulations. The molecular recognition process involves a conformational selection event. Although free C ‐glycoside access four distinct conformers in solution, hGal‐1 recognizes shape of a local minimum of compound 1 , the syn ‐ Φ / syn ‐ Ψ conformer, not the structure at global minimum. MD simulations were run to explain, in structural terms, the observed geometry of the complex.