Small-angle neutron scattering characterization of monoclonal antibody conformations and interactions at high concentrations.

摘要: Small-angle neutron scattering (SANS) is used to probe the solution structure of two protein therapeutics (monoclonal antibodies 1 and 2 (MAb1 MAb2)) their protein-protein interaction (PPI) at high concentrations. These MAbs differ by small sequence alterations in complementarity-determining region but show very large differences viscosity. The analyses SANS patterns as a function different conditions suggest that average intramolecular both not significantly altered over studied concentrations experimental conditions. Even though strong repulsive expected for due net charges low solvent ionic strength, analysis data shows effective PPI MAb1 dominated attraction volume fraction becomes negligible cannot be modeled simply spherically symmetric central forces model. It proposed an anisotropic strongly affects local interprotein leads anomalously viscosity concentrated solutions. Conversely, MAb2 displays potential throughout concentration series probed comparatively