Golgi a-mannosidase

For example, prior action of GIcNAc transferase I is necessary for the action of Golgi a-mannosidase II. 

D. A. Kuntz, C. A. Tarling, S. G. Withers, and D. R. Rose, Structural analysis of golgi a-mannosidase II inhibitors identified from a focused glycosidase inhibitor screen, Biochemistry, 47 (2008) 10058-10068. 

Employing Drosophila retaining Golgi a-mannosidase II, the binding mode of salacinol was compared with the interactions of swainsonine and kifunensine with the active site [112,113]. To date, to the best of our knowledge, the configuration of the heptitol moiety in kotalanol is still not elucidated. 

Chemical syntheses have allowed investigations of structure-activity relationships, e.g., for mannosidase inhibitors [129,130], Some potent new inhibitors have been produced such as l,4-dideoxy-l,4-imino-D-mannitol (DIM) (41), an azafuranose analogue of mannose [131] which is a good mannosidase inhibitor but unlike 1-deoxymannojirimycin it does not inhibit Golgi a-mannosidase I. 1-Deoxymannojirimycin is a more potent inhibitor of a-L-fiicosidase than of a-D-mannosidase [132], 1-Deoxyfuconojirimycin (l,5-dideoxy-l,5-imino-L-fucitol) (DFJ) (42) is a synthetic potent and specific inhibitor of human liver a-L fucosidase. 

Esters of swainsonine appear to offer therapeutic advantages in terms of specificity for Golgi a-mannosidase II, improved pharmacokinetics, and diminished side effects (143). Although 2- and 8-acyloxy esters of swainsonine were two to three orders of magnitude less active as a-mannosidase inhibitors in vitro than the parent alkaloid, the 2-butanoyl, 2-octanoyl, and 2-p-nitrobenzoyl esters, which are soluble enough to enter viable tumor cells, were as effective as swainsonine in vivo, apparently because they are hydrolyzed to swainsonine with intracellular esterases. These compounds may thus be advantageous as prodrugs. 

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