Biologies proteins degradation pathways

W., Eds., The Proteosome-Ubiquitin Protein Degradation Pathway, Springer, Berlin, 2002 Saklatvala, J. and Nagase, H., Eds., Proteases and the Regulation of Biological Processes, Portland Press, London, 2003. 

Groves, M.J. and Teng, C.D. (1992). The effect of compaction and moisture on some physical and biological properties of proteins. In Stability of Protein Pharmaceuticals, Part A Chemical and Physical Pathways of Protein Degradation, T.J. Ahem and M.C. Manning, eds. Plenum Press, New York, 311-359. 

However this polymeric chain is folded. The folding has a tremendous importance in the action ofthe protein and in its recognition by biological partners and/or by the degradation pathways. The different levels of structure are presented in Figure 1. (For more details, see for instance [i]). 

The complexity of biological macromolecules when compared with small molecule therapeutics, differences in manufacturing, and the broad variety of potential degradation pathways lead to special requirements in quality assurance and analytical testing of pharmaceutical proteins. The product-related impurities are molecular variants formed during manufacture, storage, or use, and their properties are different from the desired product with respect to activity, efficacy, and safety. 

Development of a stable antibody formulation is often challenging due to conflicting requirements of stability, cost of goods, limitations associated with the route of administration, clinical or administration convenience, and lack of robust models to predict long-term stability. One key difference in formulation development of mAbs and other proteins (referred to as NBEs, new biological entities), compared to traditional small molecules (referred to as NCEs, new chemical entities), is focus on physical stability in addition to chemical integrity of the molecule. Table 26.2 summarizes various degradation pathways for mAbs. 

The biological significance of the existence of two initiation sites for translation of poliovirus RNA In vitro depends upon whether or not these sites are utilized for translation vivo. Although all of the identified translational products do appear to be made in equal molar amounts, when corrected for alternate cleavage pathways and protein degradation (45 "47> said see chapter 7 of this book), the relative synthesis of Wg (which has not been detected free of RNA in the cytoplasmic extracts of infected cells), has not... 

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