Cottrell College Science Awards - 2015
Design and Synthesis of Anthrax Lethal Factor Inhibitors Containing a Novel and Specific Zinc Binding Group Based on a 2-2-arylsulfonamidophenylbenzimidazole Backbone
Anthrax is a virulent, nasty disease caused by Bacillus Anthracis, whose spores are naturally occurring in soils worldwide. The spores are as hardy in the environment as they are highly toxic in the body, a combination that makes anthrax a prime candidate as a weapon for bioterrorists.
“While vaccines, antibodies and antibiotics can be used to treat anthrax, many limitations have been found, including burdensome injections and side effects,” says Matthieu Rouffet, assistant professor of chemistry, Point Loma Nazarene University.
Rouffet has received a Cottrell College Science Award from Research Corporation for Science Advancement to try a different approach to stopping anthrax once it has infected a victim.
Basically, Rouffet and his students will be trying to develop potent and selective anthrax “lethal factor” inhibitors – relatively small molecules that interfere with the bacterum’s nasty behavior.
Anthrax does its dirty work primarily by secreting a toxin that disrupts the body’s signaling pathways, causes cell destruction and, fairly rapidly, circulatory shock. In order to form this toxin, anthrax uses a zinc-dependent metalloprotease called Lethal Factor. “Metalloprotease” is a type of enzyme that the body produces with a metal inside to help break down proteins into amino acids and other compounds. The fact that anthrax’s potent weapon incorporates zinc molecules, Rouffet believes, is the key to shutting it down.
His goal is to create numerous variations on relatively small, zinc-binding molecules, and to find the ones most capable of binding with anthrax lethal factor and rendering it impotent. His work will be performed in collaboration with the Seattle Structural Genomics Center for Infectious Disease.