Design Of Bridges By Krishna Raju Pdf _BEST_ Free 48
Design Of Bridges By Krishna Raju Pdf Free 48
In normal physiological condition, the back-conversion of reduced cysteine residues in SS bridges is carried out by the thioredoxin system, but, as in bacteria, eukaryotic cells have a higher thioredoxin reductase turnover and consequently larger oxidizing and reducing pools [197]. Moreover, like bacterial thioredoxin, eukaryotic thioredoxin is also found in two distinct redox forms that equally contribute to the pool of reducing power in the cytoplasm, but are differentially targeted to the oxidizing and reducing compartments of bacteria[198] and eukaryotic cells.[199] Therapeutic aggregation of thioredoxin has been proposed for treating numerous pathologies such as stroke[200] and neurodegenerative conditions.[201] This scenario prompted us to suggest the promotion of multiple disulfide bridges by recombinant thioredoxin as an alternative for rapid scale-up of therapeutic purification processes by encouraging disulfide bridge formation in cytoplasm of bacterial hosts. In such an approach, the probability of disulfide bond formation in cytoplasm of bacteria is enhanced by its specific affinity for disulfide bridges,[198] rather than its specific affinity for thioredoxin receiving passenger proteins [195]. This hypothesis has been challenged by findings showing that thioredoxin targets also disulfide-containing misfolded proteins to cytoplasmic inclusion bodies,[202] suggesting that thioredoxin functions as a chaperone by promoting the correct protein folding in the oxidized form, but not in the reduced form.[203]
Owing to the wide range of industrial applications and many examples of disulfide bond containing proteins in process development, it is of great interest to understand the physicochemical conditions that influence disulfide formation and to predict, in a controlled manner, whether disulfide linkage can be generated at all. Physicochemical conditions that influence disulfide bonding include the concentration of oxidants and reducing agents, the concentration of misfolded protein, the ionic content, pH, and temperature. Control of these variables is typically done by manipulating or adjusting their values individually or in combination. Manipulation of solute concentration includes using dialysis membranes that limit or prevent the diffusion of soluble species, osmosis, and the evaporation of water.
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