The five B-subunits (CTB5) of the Vibrio cholerae (cholera) toxin can bind to 
the intestinal cell surface so the entire AB5 toxin can enter the cell. 
Simultaneous binding can occur on more than one of the 
monosialotetrahexosylganglioside (GM1) units present on the cell surface. Such 
simultaneous binding arising from the toxins multivalency is believed to enhance 
its affinity. Thus, blocking the initial attachment of the toxin to the cell 
surface using inhibitors with GM1 subunits has the potential to stop the 
disease. Previously we showed that tetravalent GM1 molecules were sub-nanomolar 
inhibitors of CTB5. In this study, we synthesized a pentavalent version and 
compared the binding and potency of penta- and tetravalent cholera toxin 
inhibitors, based on the same scaffold, for the first time. The pentavalent 
geometry did not yield major benefits over the tetravalent species, but it was 
still a strong inhibitor, and no major steric clashes occurred when binding the 
toxin. Thus, systems which can adopt more geometries, such as those described 
here, can be equally potent, and this may possibly be due to their ability to 
form higher-order structures or simply due to more statistical options for 
binding.