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Detergent Phenomena in Membrane Protein Crystallization
Published in Hartmut Michel, Crystallization of Membrane Proteins, 1991
Most workers in the field know that micellar systems are “quite monodisperse”, but exhibit some polydispersity. The quantitative analysis is difficult. It consists of measuring the weight average and number average molecular weight of the micelles. The latter has eluded direct measurement, as vapor pressure osmometry is not sensitive enough. Polydispersity analysis of quasielastic light scattering data is particularly difficult for unimodal distributions, and observations of the asymptotic scattering in small angle techniques requires substantial surfactant concentrations, posing additioinal problems.
Uro-Angiographic Contrast Agents—The Holy Grail
Published in Christoph de Haën, X-Ray Contrast Agent Technology, 2019
The problematic reception history of osmolality measurements and interpretations involving the results is best illustrated with the situation at Nyegaard & Co A/S. In preparation for the commercialization of metrizamide, an impressive effort in toxicology and safety pharmacology, both in and outside the company, was mounted. Its dimension may be gauged looking at the more than 40 articles on metrizamide in the special journal issue that helped prepare its commercial launch (Holtermann 1973a). In the introductory paper, Holtermann for the first time reports the osmolalities of metrizamide solutions (Holtermann 1973b). At the concentration 280 mg(Iodine)/mL the osmolality was only 460 mosmol/kg, as opposed to 1,460 mosmol/kg of metrizoate meglumine at the same iodine concentration. At a concentration of 170 mg(Iodine)/mL it was isotonic with blood. Neither the method of measurement nor the temperature were specified, but the similarity of the value for the ionic product with that in the commissioned study (Børdalen, Wang, and Holtermann 1970) allows the conclusion that vapor pressure osmometry at 37° was performed. Only in 3 of the rest of the 40 papers terms related to osmotic properties appear. Only in one a control substance at the same osmolality as the metrizamide solution was included in the study. The strongest statement regarding the role of osmolality in biological effects by an author other than Almén regarded suboccipital toxicity in cats and read: “The difference in tonicity between Conray Meglumine and metrizamide must therefore, at least partially, be responsible for the less toxic effect of the latter” (Oftedal 1973).
Molecular computations of preferential interactions of proline, arginine.HCl, and NaCl with IgG1 antibodies and their impact on aggregation and viscosity
Published in mAbs, 2020
Theresa K. Cloutier, Chaitanya Sudrik, Neil Mody, Sathish A. Hasige, Bernhardt L. Trout
Timasheff and others have studied the preferential interactions of certain sugars and polyols with small proteins using preferential interaction theory.12–14 It is hypothesized that the exclusion of these osmolytes from the protein surface favors the native, folded state to minimize the exposed surface area. This may lead to a reduction in aggregation, depending on the aggregation mechanisms. The preferential interaction coefficient of antibody-excipient mixtures can be measured experimentally via vapor pressure osmometry,15 and is also accessible via simulation.11