title: Computational and experimental investigations of mono-septanoside binding by Concanavalin A: correlation of ligand stereochemistry to enthalpies of binding.
abstract: 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.
authors.affiliation: Department of Chemistry, The University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duff
authors.forename: W Sean
authors.initials: WS
authors.lastname: Fyvie
authors.forename: Shankar D
authors.initials: SD
authors.lastname: Markad
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Frankel
authors.forename: Challa V
authors.initials: CV
authors.lastname: Kumar
authors.forename: José A
authors.initials: JA
authors.lastname: Gascón
authors.forename: Mark W
authors.initials: MW
authors.lastname: Peczuh
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D003208:Concanavalin A / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008745:Methylation; D008958:Models, Molecular; D011485:Protein Binding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D002241:Carbohydrates; D008024:Ligands; D003208:Concanavalin A