Development of SMAT Technology
Due to the threat of bioterrorism, governmental agencies have stepped up
efforts to find new broad-spectrum, anti-infective agents that could be
deployed as countermeasures to biowarfare agents such as anthrax
(Bacillus anthracis) and smallpox (Variola major).
Bacillus anthracis and Variola major have unusual genomic DNA
that contains a high level of adenine-thymine (AT) base pairs (67% AT content).
Therefore, compounds that bind to AT-rich DNA should be effective therapeutics against
both of these biowarfare agents. This hypothesis was proven to be correct
using a new class of compounds referred to as small-molecule anti-genomic therapeutics (SMATs).
SMATs were designed to exhibit optimal pharmaceutical properties, and they were a
significant improvement over other DNA-binding compounds.
The SMAT research was supported by the Defense Advanced Reseach Projects
Agency (DARPA) and the United States Army Medical Research and Materiel
Command (USAMRMC). SMATs bind with high affinity in the minor groove of
AT-rich DNA sequences that are commonly found in both Bacillus anthracis
and Variola major. SMATs were also shown to be effective against
drug-resistant pathogens such as malaria (Plasmodium falciparum) and
gram-positive bacteria (e.g. Streptococcus pneumoniae). Therefore, SMATs are low-cost,
multi-use therapeutics that could offer substantial logistical and cost benefits to the military.
The development of SMATs encompassed an approach that focused on improving the
tolerability, pharmacokinetics, and efficacy of these compounds. The SMAT program was
very successful and received 5 years of government funding. The biodefense program was
terminated voluntarily due to the sale of Genesoft Pharmaceuticals, and Azee Pharmaceuticals
was formed to expand the clinical applications of the SMAT technology and to commercialize
SMAT products for public markets.
