Computational and experimental investigations of mono-septanoside binding by Concanavalin A: correlation of ligand stereochemistry to enthalpies of bindingElectronic supplementary information (ESI) available: 1H and 13C NMR spectra for all newly reported compounds. Computed QM/MM structures not shown in the main text are provided. Further details on the thermodynamic cycle used in our calculations and approximations are also provided. See DOI: 10.1039/c0ob00425a

• Main Authors: Duff Jr, Michael R, Fyvie, W. Sean, Markad, Shankar D, Frankel, Alexandra E, Kumar, Challa V, Gascón, José A, Peczuh, Mark W
• Format: Journal Article
• Language: English
• Published: 09.12.2010
• DOI: 10.1039/c0ob00425a
• ISSN: 1477-0520

Structure-energy relationships for a small group of pyranose and septanose mono-saccharide ligands are developed for binding to Concanavalin A (ConA). The affinity of ConA for methyl "manno" β-septanoside 7 was found to be higher than any of the previously reported mono-septanoside ligands. Isothermal titration calorimetry (ITC) in conjunction with docking simulations and quantum mechanics/molecular mechanics (QM/MM) modeling established the specific role of binding enthalpy in the structure-energy relations of ConA bound to natural mono-saccharides and unnatural mono-septanosides. An important aspect in the differential binding among ligands is the deformation energy required to reorganize internal hydroxyl groups upon binding of the ligand to ConA. Isothermal titration calorimetry (ITC) in conjunction with docking simulations and QM/MM established structure-energy relationships between ConA and natural methyl pyranosides and unnatural methyl septanosides.