To stabilize a transition state.
Inspection of the active sites of the many enzymes whose structures are known at high resolution leads to the unsurprising conclusion that an enzyme may provide an environment that exquisitely stabilizes the transition state for an elementary catalytic step that is expected to be difficult. In an effort both to mimic such an environment and to have the opportunity of investigating the thermodynamic and kinetic consequences of juxtaposing polar and non-polar loci in the same molecule, we have synthesized several specifically functionalized alpha-cyclodextrins. One of these is designed to stabilize the trigonal bipyramidal transition state for an in-line displacement at the phosphorus of a phosphate monoester. This cyclodextrin contains three symmetrically disposed ammonium groups on the 'top' (at C-6) of the hydrophobic cavity formed by the hexa-glucose torus and the remaining 15 hydroxy groups are methylated. The thermodynamic consequences of adjacent hydrophobic and hydrogen-bonding and/or electrostatic binding sites are investigated using several charged and uncharged ligands. The feasibility of building host species explicitly to stabilize reaction transition states is discussed.
D003912:Dextrins; D004798:Enzymes / Q000378:metabolism; D006860:Hydrogen Bonding; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008968:Molecular Conformation; D009943:Organophosphorus Compounds; D011485:Protein Binding; D011487:Protein Conformation; D013213:Starch; D013816:Thermodynamics
D003912:Dextrins; D004798:Enzymes; D008024:Ligands; D009943:Organophosphorus Compounds; D013213:Starch