| Abstract: |
Protein-protein interactions are central to solubility and viscosity, two properties important in biopharmaceutical development and formulation. Both lower solubility and increased viscosity result from weak attractive protein-protein interactions. Hence, it would be helpful to have a rigorous means to assess attractive interactions.
A thermodynamically rigorous method for assessing the attraction between proteins is presented. This method requires only two readily made measurements and simple algebraic calculations. The quantity that results may be used to assess and rank the suitability of proteins and solvents for development and formulation.
Molecular interactions may be repulsive or attractive. For a homogeneous solute, the repulsive interactions are described by the second virial coefficient, B22, which is the sum of an entropic (excluded volume) and an enthalpic (electrostatic) contribution. Only charge-charge repulsion contributes to B22.
The sum of two easily measured quantities, the Stokes radius Rs(as 4/3·π·RS3) and the effective charge zeff (as zeff = u·f), where u is the electrophoretic mobility and f is the ordinary translational diffusion constant provide the maximum value for B22, B22max. Measured values of B22 must be less than B22max or else either RS or zeff is in error. However, measured values of B22 will be less than B22max if there are attractive inter-molecular forces. The ratio B22measured/B22max provides a thermodynamically rigorous measure of the inter-particle attractive interactions that is predictive of which molecule/solvent combinations will provide the highest solubility and lowest viscosity. |
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