Glycoprotein Processing Inhibitors

A number of mannosidase inhibitors have been isolated from various plants and fungi, and the specificity and activity of many of these inhibitors has been outlined in Table 1. The first glycoprotein processing inhibitor to be identified was the in-dolizidine alkaloid, swainsonine whose structure is presented in Figure 1B. Swain-sonine was shown to specifically inhibit plant and animal mannosidase II [78]. This alkaloid also inhibits lysosomal a-mannosidase and jack bean a-mannosidase, but... 

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. 

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... 

A USDA group was struck by the similarity in structure between the two hydroxylated indolizidines 95 and 96, and was led to examine the effect of castanospermine on hydrolytic enzymes. The American workers found it was a powerful inhibitor of both a- and [3-glucosidases [1151 it was further shown to inhibit glycoprotein processing [116], which in... 

Elbein AD, Solf R, Dorling PR, Vosbeck K (1981) Swainsonine an inhibitor of glycoprotein processing. Proc Natl Acad Sci USA 78 7393-7397... 

Madin-Darby canine kidney cells, inhibitor of processing of, 353 viral glycoprotein, 16, 353 viral glycoprotein processing... 

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