Protease degradation

S., IwAKURA, M., and Matouschek, A. ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal. Mol Cell 2001, 7, 627-37. 

Increased in vivo stability due to resistance to protease degradation. " ... 

However, as important as the Hu and Bentley Model is the stepwise approach to process optimisation that Hu and Bentley have reported [33]. The focus on quantitative analysis of protease degradation of the product over time, along with the similar approach followed by Cruz et al. [25], also indicate new directions to follow in mathematical modelling regarding product expression optimisation. 

The vitro potencies are moat likely to reflect relative receptor affinities since protease degradation in this system is minimized. Improved metabolic stability should, therefore, not appear as enhanced potency. 

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

Proteases degrade ingested proteins in the stomach and small intestine. Most proteases are initially synthesized as inactive zymogens. 

Throughout the purification process we must have a convenient means of assaying for the desired protein, so we can know the extent to which it is being enriched relative to the other proteins in the starting material. In addition, a major concern in protein purification is stability. Once the protein is removed from its normal habitat, it becomes susceptible to a variety of denaturation and degradation reactions. Specific inhibitors are sometimes added to minimize attack by proteases on the desired protein. During purification it is usual to carry out all operations at 5°C or below. This temperature control minimizes protease degradation problems and decreases the chances of denaturation. 

Proteases degrade the unbound antibody molecules. (5) The degraded products reside in the lysosome part. (6) The intact IgG molecules bound to Fc-Rn are transported to the cell membrane where they can be returned to the extracellular space. 

Protein aggregates [107, 109, 121] or dye crystals [122-126] can serve as templates for LbL polyelectrolyte adsorption. Chymotrypsin aggregates encapsulated by PSS and PAH deposition contain a high protein amount and the enzyme keeps its bioactivity [107], The aggregates prepared in this manner have high incorporation efficiency and a protein content of 50-70% [109]. An encapsulated catalase has been shown to be stable against protease degradation [121],... 

Proteases are released when cells are lysed, and this can lead to the degradation of the desired protein, if one does not work rapidly enough, or if the temperature is allowed to rise above 0 °C (Deutscher 1990b Beynon and Oliver 1996). It is nevertheless difficult to avoid protease degradation in the early stages of a purification, particularly for sensitive proteins, and/or in cells or tissues (e.g., the pancreas) where proteases are particularly abundant, unless protease inhibitors are added. 

Figure 2 Bacillus subtiHs S2P-like protease SpolVFB and sporulation. When the mother cell engulfs the forespore, a signaling pathway that involves the transcription factor is initiated in the forespore that triggers the synthesis of the IVB serine protease. This protease degrades SpolVFA, which along with BofA serves to inhibit SpolVFB. With the inhibition of the S2P-like protease released, SpolVFB cleaves pro-c, which allows this transcription factor to signal in the mother cell for more factors needed for spore maturation.

Proteases degrade the proteins to free amino acids and oligopeptides, thus imparting sweet, sour and mainly a bitter taste to the product. Further reactions lead to the corresponding Strecker aldehydes 2-methylbutanal and 3-methylbutanal with a pungent, malty, cocoa note. 

Bacillus subitilis Second best studied bacteria Gram positive—no outer membrane—excretes proteins Problem excreting some foreign proteins Makes large amounts and varieties of proteases (degrades proteins rapidly) More difficult to manipulate genetically owing to limited vectors and promoters Instability of plasmids more problematic than E. coli... 

The structure of the PG molecule renders it vulnerable to degradation by MMPs, since cleavage of only one or two peptide bonds can destroy its function. As a result, PG turns over more rapidly than collagen. When protease degradation of PGs is induced experimentally, cartilage maintains its shape but loses elasticity. 

Proteases Degradation of proteins C and N aquisition Present in bacteria... 

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