A pentavalent inhibitor for cholera toxin
Research reports the first pentavalent inhibitor for cholera toxin that exactly matches the pentavalent structure of the cholera toxin binding domain.
Cholera still represents a serious health problem in areas of the developing world where there is a lack of clean water and proper sanitation. It causes an acute intestinal infection that in severe cases can be fatal.
An international collaboration of scientists developed an inhibitor based on the pentasaccharide GM1, which is the natural target ligand for the cholera toxin on cellular membranes of the infected hosts’ intestinal epithelial surface. Previous work has combined either pentavalent scaffolds with simpler sugars, or non-pentavalent scaffolds with GM1, but this is the first example of an inhibitor that is both pentavalent and uses the natural ligand for cholera toxin.
The scientists synthesised the inhibitor via enzymatic synthesis of GM1 and coupling to a calix[5]arene scaffold. Tests to determine the potency of the inhibitor showed it to have the highest relative inhibitory potency documented for cholera toxin inhibitors so far.
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