The present invention features Bacillus anthracis lethal factor substrate and assays employing the substrate to measure lethal factor activity and to screen for compounds affecting lethal factor activity (Figure 1).
One method comprises administering an effective amount of wild-type, or preferably a mutated form of, B. anthracis lethal factor (LF) or an immunogenic fragment thereof to the subject.
The preferred antigenic epitopes correspond to immunogenic regions of protective antigen, lethal factor or edema factor, either individually or in combination.
Anthrax toxin, comprising of protective antigen (PA), lethal factor (LF) and edema factor (EF) is a major virulent factor of B.anthracis.
These proteins bind to human tyrosine kinase Hck and promote apoptosis caused by the stimulus by tumor lethal factor.
The protective efficacy of PA is greatly increased if small quantities of LF or EF are incorporated into the vaccines.
An ideal vaccine against anthrax should contain PA, LF and EF together, but this combination would be toxic.
Therefore, the biologically inactive mutant preparations of PA, LF and EF may be used together for better immunoprotection.
Libraries of these compounds are also useful as substrates for screening methods to identify LF inhibitors.
This invention further relates to a process for synthesis of potent LF-inhibitors for the treatment of anthrax.
This invention relates to a process for preparing optically active α -amino acid substrates which are used to make potent lethal factor (LF) inhibitors for the treatment of anthrax.