Ellagitannins with Glucopyranose Cores Have Higher Affinities to Proteins than Acyclic Ellagitannins by Isothermal Titration Calorimetry.

The thermodynamics of the interactions of different ellagitannins with two proteins, namely, bovine serum albumin (BSA) and gelatin, were studied by isothermal titration calorimetry. Twelve individual ellagitannins, including different monomers, dimers, and a trimer, were used. The studies showed that several structural features affected the interaction between the ellagitannin and the protein. The interactions of ellagitannins with proteins were stronger with gelatin than with BSA. The ellagitannin-gelatin interactions contained both the primary stronger and the secondary weaker binding sites. The ellagitannin-BSA interactions showed very weak secondary interactions. The ellagitannins with glucopyranose cores had stronger interaction than C-glycosidic ellagitannins with both proteins. In addition, the observed enthalpy change increased as the degree of oligomerization increased. The stronger interactions were also observed with free galloyl groups in the ellagitannin structure and with higher molecular flexibility. Other smaller structural features did not show any overall trend.

Binding of an Oligomeric Ellagitannin Series to Bovine Serum Albumin (BSA): Analysis by Isothermal Titration Calorimetry (ITC).

A unique series of oligomeric ellagitannins was used to study their interactions with bovine serum albumin (BSA) by isothermal titration calorimetry. Oligomeric ellagitannins, ranging from monomer to heptamer and a mixture of octamer-undecamers, were isolated as individual pure compounds. This series allowed studying the effects of oligomer size and other structural features. The monomeric to trimeric ellagitannins deviated most from the overall trends. The interactions of ellagitannin oligomers from tetramers to octa-undecamers with BSA revealed strong similarities. In contrast to the equilibrium binding constant, enthalpy showed an increasing trend from the dimer to larger oligomers. It is likely that first the macrocyclic part of the ellagitannin binds to the defined binding sites on the protein surface and then the "flexible tail" of the ellagitannin coats the protein surface. The results highlight the importance of molecular flexibility to maximize binding between the ellagitannin and protein surfaces.