Conformational Selection in Glycomimetics: Human Galectin‐1 Only Recognizes syn‐Ψ‐Type Conformations of β‐1, 3‐Linked Lactose and Its C‐Glycosyl Derivative. Issue 43 (17th September 2013)

• Record Type: Journal Article
• Authors: Vidal, Paloma; Roldós, Virginia; Fernández‐Alonso, María del Carmen; Vauzeilles, Boris; Bleriot, Yves; Cañada, F. Javier; André, Sabine; Gabius, Hans‐Joachim; Jiménez‐Barbero, Jesús; Espinosa, Juan Félix; Martín‐Santamaría, Sonsoles
• Is Part Of: Chemistry. Volume 19:Issue 43(2013)
• Page Start: 14581
• Page End: 14590
• Publication Date: 2013-09-17
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201301244
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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‐<italic>C</italic>‐(1→3)‐Glcβ‐<italic>O</italic>Me (<bold>1</bold>) 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 <italic>C</italic>‐glycoside access four distinct conformers in solution, hGal‐1 recognizes shape of a local minimum of compound <bold>1</bold>, the <italic>syn</italic>‐<italic>Φ</italic>/<italic>syn</italic>‐<italic>Ψ</italic> conformer, not the structure at global minimum. MD simulations were run to explain, in structural terms, the observed geometry of the complex.</p> </abstract>