Glycosylation, effect proteins

Carbohydrates play a major role in protein bioactivity, bioavailability, and antigenicity therefore, the understanding of the glycosylation of protein molecules is very important in the development of effective glycoprotein therapeutics.172 In recent years, there has been considerable activity in the development of simple, rapid, and reliable separation methods for the analysis of... 

Thus, the effects of glycosylation inhibitors on intact cells may also be studied best with virus-infected cells. Before release of virus, the glycoproteins are detected in the water-insoluble, membranous fraction. Furthermore, the lipid-linked oligosaccharides may be rather specifically extracted from whole cells, and monosaccharide-lipids may also be determined.3-116 It is thus seen that the various tools of virology and of lipid and carbohydrate biochemistry have proved productive in establishing the mode of action of inhibitors of lipid-depen-dent glycosylation of proteins. 

In contrast to these results, 25-hydroxycholesterol (and also, 20-hy-droxycholesterol, 7-ketocholesterol, and diosgenin) in aortic, smooth-muscle cells effectively blocks the incorporation of acetate into lipid-linked oligosaccharides (and, also, into cholesterol7). Thus, less of the lipid-linked oligosaccharides were available for glycosylation of proteins. In harmony with the presumed, inhibitory mechanism was the observation that incorporation of mevalonate into lipid-linked oligosaccharides was not inhibited, and that mevalonate itself (the product formed by HMG-CoA reductase from HMG-CoA and NADPH) could reverse the inhibition of glycosylation of protein (see Scheme 1). 

Seitz, O. (2000) Glycopeptide synthesis and the effects of glycosylation on protein structure and activity. Chem. BioChem. 1, 214-246. 

Induction of mRNAs for several other specific rat hepatic proteins by GH has also been demonstrated [81-83]. The effect could be demonstrated in vivo and in vitro and involved a relatively rapid induction with a 5-fold increase in mRNA levels within 4 h of the administration of GH, although synergism with cortisol (possibly and/or thyroxine) was necessary for a maximal response [83]. cDNAs corresponding to two of the induced proteins have been cloned [82,83] and found to have sequences homologous to those of a known family of serine protease inhibitors. One of these proteins was shown to be secreted as a heavily glycosylated serum protein, and to have potent anti-trypsin activity [83]. Regulation of the production of this protein by GH was shown to occur mainly at the transcriptional level [83]. 

Figure 4 Effect of degree of glycosylation on protein biophysics, (a) The effect of degree of glycosylation on thermal stability as measured either by the change in TF relative to the unmodified protein (ArF=(TF lycosylated-TFunslycosylated)/rFun l) cos) lated) or by the degree of folding (calculated at the temperature at which the folded state of the unmodified protein is 50% populated), (b) The effect of degree of glycosylation on the size of folded and unfolded conformations.

Shental-Bechor, D., Levy, Y. Effect of glycosylation on protein folding A close look at thermodynamic stabilization. Proc. Natl. Acad. Sci. U.S.A. 2008,105, 8256-61. 

Bernstein, R. E., Some functional effects of non-enzymatic glycosylation of proteins. Proc. Ann. Congr. Pharmacol. Physiol. Soc. S. Afr., p. 69 (1984). 

Inhibition of Protein Glycosylation Effects of Nucleotide Deoxysugars on the Formation of Glycosylated Lipid Intermediates , Archives of Biochemistry and Biophysics, 206, 65-71... 

Many diabetics have long-standing elevated blood glucose levels. In the open-chain form, glucose condenses with the amino groups of proteins. This glycosylation of proteins may cause some of the chronic effects of diabetes. 

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