Chemistry Reference
In-Depth Information
Figure 28.2
Some naturally occurring glycosidase (carbohydrate - trimming enzyme) inhibitors.
Figure 28.3
Structure of sialyl - Le
x
.
28.2
Viral Infections: HIV - 1 and Infl uenza
Carbohydrate-based therapies are being used to treat a range of viral infections,
including AIDS and infl uenza. In these cases the infective pathways again rely on
carbohydrate-protein interactions for their initiation, so methods that disrupt the
synthesis and/or interaction of the carbohydrates are likely to offer hope for treat-
ment of the diseases (see Chapter 17.2 for details of viral lectins and Chapter 4.1
for strategies to block viral adhesion). For example, with HIV-1, an unusual gly-
coprotein gp120 is displayed on the viral surface. More than 50% of the weight of
gp120 has been ascribed to the carbohydrates and, of these carbohydrates, 24 have
been identifi ed as
N
-linked oligosaccharides, with 11 predominantly consisting of
mannose glycans or hybrids thereof [8]. gp120 plays an important role in the infec-
tive process for the HIV as it is involved in the initial binding of the virus to lectins
on the T cells. At present, clinical treatments for HIV-1 have been developed based
upon inhibition of the HIV-1 reverse transcription enzyme and the HIV-1 protease
enzyme that cleaves polyproteins into smaller functional protein units. Carbohy-
drate-based inhibitors have included the nucleoside analog reverse transcriptase
