The peptide, called D6R (hexa-D-arginine amide), is a potent, stable, small molecule inhibitor of furin. Bacteria produce a number of toxins which rapidly enter and kill cells. In anthrax, the lethal factor toxin must bind to another part of the anthrax toxin, called the PA molecule, before it can enter and destroy a cell. But before binding can occur, the PA molecule produced by the bacteria must be made smaller. Furin, a protein-cutting enzyme or protease, which sits on the outside of cells, cuts the PA molecule, enabling the lethal factor toxin to attach to it. Lethal factor toxin cannot bind to PA that has not already been cut by furin; therefore, without cut PA, lethal factor toxin loses the ability to bind to and enter the cell, and becomes harmless.
Working on the theory that if the action of furin could be blocked, the toxins would not be activated and therefore unable to kill cells, the research team set out to make a peptide that would suppress furin activity. In collaboration with a research group in California (Torrey Pines Institute for Molecular Studies), the LSUHSC group developed the furin inhibitor, D6R. The LSUHSC research group working on anthrax under the direction of Dr. Iris Lindberg, Professor of Biochemistry, included past postdoctoral fellows Dr. Miroslav S. Sarac and Dr. Angus Cameron.
The LSUHSC research scientists examined the therapeutic potential of D6R against Pseudomonas aeruginosa exotoxin, both in cell culture and in live animals (mice). Various concentrations of D6R were tested, with no apparent side effects, regardless of dose. The survival rate of cells in culture 48 hours after treatment with D6Rgiven at the
Contact: Leslie Capo
Louisiana State University Health Science Center