Thermodynamic analysis of the molecular interactions between amyloid β-protein fragments and (-)-epigallocatechin-3-gallate

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) has been proven effective in preventing the aggregation of amyloid β-protein 42 (Aβ42), and the thermodynamic interactions between Aβ42 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 Aβ42 and EGCG, three Aβ42 fragments (i.e., Aβ1-16, Aβ1-30, and Aβ31-42) 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 Aβ42 and EGCG, hydrogen bonding mainly happens in Aβ1-16 while hydrophobic interaction mainly happens in Aβ17-42. It is found that when Aβ42 and its fragments are saturated by EGCG, their thermodynamic parameters have linear relationships. The saturated binding stoichiometry (N(s)) for Aβ42 is the sum of the N(s) values for Aβ1-30 and Aβ31-42, while ΔH(s), ΔS(s), and ΔG(s) for Aβ42 are half the sum of the values for Aβ1-30 and Aβ31-42. The result suggests that there are no specific interactions and binding sites in the Aβ42 and EGCG binding. The orders of ΔH(s) and TΔS(s) values for the Aβ fragments are determined as Aβ17-42 > Aβ31-42 > Aβ1-30 > Aβ1-16. Moreover, there is significant enthalpy-entropy compensation in the binding of EGCG to Aβ42 and its fragments, resulting in insignificant change of ΔG with the change of the solution environment. The research has shed new light on the molecular mechanisms of the interactions between EGCG and Aβ42.