Understanding the mechanism for sucroseinduced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucroseinduced restriction of rhIL-1ra conformational f luctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.

Xenon and isoflurane inhibit NMDA receptors by binding at the same site as the coagonist glycine. This finding may have important implications for general anesthesia and neuroprotection. Neuroprotectants that act at the glycine site of the NMDA receptor antagonists are well tolerated in patients, being devoid of psychotomimetic side effects, and the mechanism of inhibition may play a role in their clinical profile.

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We present adsorption isotherms, phase diagrams, and density profiles for a Lennard-Jones fluid confined to a cylindrical pore. In particular, we concentrate on the gas–liquid transition in the pore (capillary condensation). We compare simulations for a series of radii and different temperatures with mean field density functional theory (MFT). Two forms of MFT are considered, the simple local density approximation (LDA) and Tarazona’s nonlocal or smoothed density approximation (SDA). We find that the SDA provides a quite accurate description of fluid structure in the pore and that it produces phase diagrams in good agreement with the simulation data. For larger radii and temperatures T/Tc≳0.6 the SDA shows steep rises in adsorption close to the transition. This strongly affects the shape of the coexistence curve in the T, ρ̄ plane. Here ρ̄ is defined as the average density inside the pore. This behavior is confirmed by the simulation. In contrast, LDA gives a poor representation of the fluid structure and this underlies the failure to reproduce the phase diagrams and adsorption isotherms found with SDA or simulation. For extremely small radii (R*≈1) the simulation adsorption isotherms are smooth, and for not too low a temperature they are accurately described by an approach which starts from the potential distribution theorem and uses perturbation theory for the true one-dimensional fluid.