Conformational Selection in Glycomimetics: Human Galectin‐1 Only Recognizes syn‐Ψ‐Type Conformations of β‐1,3‐Linked Lactose and Its C‐Glycosyl Derivative |
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| Authors: | Dr Paloma Vidal Dr Virginia Roldós Dr María del Carmen Fernández‐Alonso Dr Boris Vauzeilles Prof Dr Yves Bleriot Prof Dr F Javier Cañada Dr Sabine André Prof Dr Hans‐Joachim Gabius Prof Dr Jesús Jiménez‐Barbero Dr Juan Félix Espinosa Dr Sonsoles Martín‐Santamaría |
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| Institution: | 1. Discovery Chemistry Research and Technologies, Centro de Investigación Lilly, Avenida de la Industria 30, 28108 Alcobendas, Madrid (Spain);2. Chemical and Physical Biology, CIB‐CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain);3. CNRS and Université Paris‐Sud, Glycochimie Moléculaire et Macromoléculaire, ICMMO, UMR 8182, 91405 Orsay (France);4. Laboratoire SRSN, Université de Poitiers, 40, avenue du Recteur Pineau, 86022 Poitiers (France);5. Institut für Physiologische Chemie, Tier?rztliche Fakult?t, Ludwig‐Maximilians‐Universit?t München, Veterin?rstr. 13, 80539 München (Germany);6. Chemistry and Biochemistry Department, Facultad de Farmacia, Universidad CEU San Pablo, 28668‐Boadilla del Monte, Madrid (Spain) |
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| Abstract: | 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‐OMe ( 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. |
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| Keywords: | conformation analysis glycoconjugates molecular modeling NMR spectroscopy structure– activity relationships |
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