Glycoprotein processing

Table 47-11. Some factors affecting the activities of glycoprotein processing enzymes.

Humans and animals are affected by genetic diseases that occur as a result of inhibition of glycoprotein-processing enzymes (reviewed by James et al., 2004). These diseases are collectively known as lysosomal storage diseases. The animal diseases, genetic or induced, have counterparts in humans. For example ... 

Interferons—a family of glycoproteins processed by macrophages—also are widely used as immunostimulants (a -interferons), made in macrophages and fibroblasts (j3-interferons), made in lymphocytes (7-interferons), which are named for their ability to react with viral RNA and affect protein synthesis. Commercially accessible a-, fi-, and y-interferons are currently used in medicine. Practically the only purely synthetic immunos-timulant drug that is used is levamisole, which was initially proposed as an anthelminthic agent, and it is currently widely used as such. 

In contrast to the inactive parent compound 2, inhibition of glycoprotein-processing oc-glucosidases was also found by Butters and coworkers for 1-deoxynojirimycin derivatives having phenylalkyl substituents of medium chain lengths (C4—C6) at the ring nitrogen atom.359... 

D. S. Alonzi, R. A. Dwek, and T. D. Butters, Improved cellular inhibitors for glycoprotein processing a-glucosidases Biological characterisation of alkyl- and arylalkyl-N-substituted deoxynojirimycins, Tetrahedron Asymmetry, 20 (2009) 897-901. 

Tropea, J E, Molyneux, R J, Kaushal, G P, Pan, Y T, Mitchell, M, Elbein, A D, Austrahne, a pyrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing. Biochemistry, 28, 2027-2034, 1989. 

Sunkara, P S, Bowlin, T L, Liu, P S, Sjoerdsma, A, Antiretroviral activity of castanospermine and deoxynojirimycin, specific inhibitors of glycoprotein processing, Biochem. Biophys. Res. Commun., 148, 206-210, 1987. 

Wright, P S, Cross-Doersen, D E, Schroeder, K K, Bowlin, T L, McCann, P P, Bitonti, A J, Dismption of Plasmodium falciparum-infected erythrocyte cytoadherence to human melanoma cells with inhibitors of glycoprotein processing, Biochem. Pharmacol, 41, 1855-1861, 1991. 

The pronounced and diverse biological activity of (- )-swainsonine (162) stems from its potency as an inhibitor of a-mannosidases, and its consequent ability to alter the course of glycoprotein processing. Mannosidases partially or wholly characterized during, or detected in, recent inhibition studies with the alkaloid include a-D-mannosidases in the parasite Trypanosoma cruzi 145,146) and in various insects 147,148), a murine lysosomal a-mannosidase 149), and a-mannosidases 1 and II from Vigna umbellata (rice beans) 150). The alkaloid was used to differentiate... 

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