Ionic strength effects on protein

Yang, A. and B. Honig. (1994). Structural origins of pH and ionic strength effects on protein stability. Acid denaturation of sperm whale apomyoglobin. J. Mol. Biol. 237 602-14. 

A.-S. Yang and B. Honig, /. Mol. Biol., 237, 602 (1994). Structural Origins of pH and Ionic Strength Effects on Protein Stability. Acid Denaturation of Sperm WTiale Apomyoglobin. 

It is also important to point out that the direction of the ionic strength effect on rate constants does not always correlate with the protein net charge. Thus, in reactions with FMN [47] and flavodoxin [48], three species of cytochrome C2 having net charges of —7, 0 and -1-2 all show attractive electrostatic interactions during ET with these negatively charged species. The reason for this behavior lies in the fact... 

Fig. 1. Effect of pH on the corrected sedimentation constant of conalbumin at ionic strength 0.1, protein concentration 1.1—1.3 g./lOO ml. , conalbumin prepared by electrophoresis—convection O. conalbumin prepared by the acid precipitation method Q, conalbumin prepared by electrophoresis—convection, exposed for 1 hr. to pH 2—3 before sedimentation at pH 5.2 A, conalbumin prepared by the acid precipitation method, exposed for 1 hr. to pH 2.5—3.4 before sedimentation at pH 4.5—7.5. (Arch. Biochem. Biophys. 61, 51 [1956]).

The present results suggest that PL-cellulose spherical particles can reduce the concentrations of natural LPS to 1 EU/mL or lower in drugs and fluids used for intravenous injection, at a neutral pH and ionic strengths of fi=0.05-0.4. These processes did not affect the recovery, even of acidic proteins such as BSA. The high LPS-adsorbing activity of the PL cellulose is possibly due to the cationic properties of the ligand and its suitable hydrophobic properties. The high LPS selectivity of the particles with small pore size is due to the size-exclusion effects on protein molecules. By contrast, that of the particles with... 

Once a range of suitable pH and ionic strength are selected, the effect on protein stability is evaluated for the final selection of an optimal formulation pH. Only when the optimal pH and addition of common salts do not render the desired solubility are other additives considered. This adds to the complexity of the formulation and the challenge of maintaining stability. Recently, an empirical approach to determine protein phase diagrams using various biophysical techniques has been used to facilitate identification of optimal formulation conditions (Fan etal., 1995). 

On the whole, however, the usual relation— absorption of heat on solution and increase of solubility with temperature— is found much more commonly in protein systems, especially at low ionic strengths. Differ t proteins often differ markedly in heat of solution. The classical method of preparation of edestin involved its crystallization by the gradual cooling of a very warm salt solution of the protein. Marked differential effects of temperature on solubility have been observed for different components among the globulins of normal plasma, notably for y- obulin, and fibrinogen, and have been used already in certain procedures, especially for the purification of fibrinogen (Part VI). 

The ionic strength at which protein-protein complexes disintegrate is in general lower than for polyelectrolyte complexes. Probably because of the low charge density of the protein molecules and their less optimal packing within the complex. In some systems, an increase in temperature results in disintegration of the precipitates [82, 88]. This effect can be attributed to hydrophobic interactions and hydrogen bond formation between the amino acids. These interactions are known to be dependent on the temperature. 

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