Thermodynamic Analysis of the Molecular Interactions between Amyloid β-Protein Fragments and (-)-Epigallocatechin-3-gallate

(-)-Epigallocatechin-3-gallate (EGCG) has been proven effective in preventing the aggregation of amyloid beta-protein 42 (A beta 42), and the thermodynamic interactions between A beta 42 and EGCG have been studied in our previous work (J. Phys. Chem. B 2010, 114, 11576). Herein, to further probe the interactions between different regions of A beta 42 and EGCG, three A beta 42 fragments (i.e., A beta 1-16, A beta 1-30, and A beta 1-42) were synthesized, and the thermodynamic interactions between each of the fragments and EGCG at different EGCG and salt concentrations were investigated by isothermal titration calorimetry. The results indicate that, although hydrogen bonding and hydrophobic interaction are both involved in the interactions between A beta 42 and EGCG, hydrogen bonding mainly happens in A beta 31-16 while hydrophobic interaction mainly happens in A beta 17-42. It is found that when A beta 42 and its fragments are saturated by EGCG, their thermodynamic parameters have linear relationships. The saturated binding stoichiometry (N-s) for A beta 42 is the sum of the Ns values for A beta 1-30 and A beta 31-42, while Delta H-s, Delta S-s, and Delta G(s) for A beta 42 are half the sum of the values for A beta 1-30 and A beta 31-42. The result suggests that there are no specific interactions and binding sites in the A beta 42 and EGCG binding. The orders of Delta H-s and T Delta S-s values for the A beta fragments are determined as A beta 17-42 > A beta 31-42 > A beta 1-30 > A beta 1-16. Moreover, there is significant enthalpy entropy compensation in the binding of EGCG to A beta 42 and its fragments, resulting in insignificant change of Delta G with the change of the solution environment. The research has shed new light on the molecular mechanisms of the interactions between EGCG and A beta 42.