Thermodynamic assessment of the stability of thrombin receptor antagonistic peptides in hydrophobic environments

In this paper, a general procedure is described to determine thermodynamic parameters associated with the interaction of thrombin receptor antagonistic peptides (TRAPs) with immobilized nonpolar ligands. The results show that these interactions were associated with nonlinear van't Hoff dependencies over a wide temperature range. Moreover, changes in relevant thermodynamic parameters, namely the changes in Gibbs free energy of interaction, ΔG_assoc ⁰, enthalpy of interaction, ΔH_assoc ⁰, entropy of interaction, ΔS_assoc ⁰, and heat capacity, ΔC_p ⁰, have been related to the structural properties of these TRAP analogs. The implications of these investigations for the design of thrombin receptor agonists/antagonists with structures stabilized by intramolecular hydrophobic interactions are discussed.