Glycosyltransferase inhibitors

Compain, P. et al. Carbohydrate Mimetics-Based Glycosyltransferase Inhibitors. 2001 [24]... 

Compain, P, Martin, O R, Carbohydrate mimetics-based glycosyltransferase inhibitors, Bioorg. Med. Chem., 9, 3077-3092, 2001, and references cited therein. 

R.R. Schmidt and co-workers designed and synthesized a novel class of glycosyltransferase inhibitors. The key synthetic steps involve an Arbuzov reaction followed by a coupling with uridine-5 -morpholidophosphate as the activated derivative. 

Sophisticated feeding strategies based on N-acetyhnannosamine (ManNAc) [18] supplementation or addition of specific glycosyltransferase inhibitors [19] Wata-nabe and co-workers reported the capacity of High Five for interferon-y N-gly-can sialylation following cultivation of these insect cells in the presence of an hexosaminidase inhibitor (2-AND). 

The rational design of glycosyltransferase inhibitors has been on substrate mimicry. For example, Lowary and coworkers synthesized 3-amino-3-deoxy(Fucal-2)Gal/3-0(CH2)7CH3 as a competitive inhibitor of the blood group A A-acetylgalactosaminyltransferase (Figure 16(i)). The administration of this compound to cells afforded only a modest reduction of the blood group A determinant expression, which was attributed to... 

The phase transfer-catalysed synthesis of carbohydrate 1,2-epoxyphosphonates (e.g. 2) has been achieved, and the C-glycoside phosphonate 3 has been described. The related phosphonate 4 has been synthesized from D-mannose as an analogue of L-/nyo-inositol 1,4,5-trisphosphate and the glycosyl phosphonate 5 has been prepared as an analogue of KDO. Some glycal methylphosphonates (e.g, 6) have been synthesized as precursors to potential glycosyltransferase inhibitors (see Chapter 13 for details of synthesis), and some 2, 3 -dideoxy-3 -C-phosphononucleosides are mentioned in Chapter 20. 

Scheme 1. Some naturally occurring glycosyltransferase inhibitors.

Another group of inhibitors that could be very important tools in Glycobiology are glycosyltransferase inhibitors that are able to permeate intact cells and that are specific for individual enzymes such as GlcNAc transferase I or GlcNAc transferase... 

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