Principal Investigator (PI)
The Foundation is providing £190,691 in support.
Jie Shi - Torben Heiden
Our approach towards Shigella involves the Shiga toxin as its target. This toxin causes serious disease,and is clearly on the rise in the dominant Shigella species in the developing world. It is an AB5 toxin that binds to multiple copies of a carbohydrate moiety expressed on the cell surface. We intend to design and synthesize the optimal binding moieties for toxin binding. These designs are based on our previously successful rigid spacer design for bridging binding sites and on our approach to inhibit the related Cholera AB5 toxin at picomolar concentrations. The focus is on intercepting the toxin in the blood stream. The Shiga toxin is an excellent target as it should be amenable to very potent inhibition and a demonstration of in vivo susceptibility has already been made. We intend to design and synthesize the compounds in Utrecht (UU) and explore their potency and activity at OL.