Dual-Target Approach
A serious medical problem facing society has been the emergence of resistance to all of the major classes of antibiotics. Bacteria develop point mutations in the gene encoding the protein targeted by an antibiotic, and eventually evolve resistance by finding mutations that lower the potency of the drug at its target. To circumvent this process and make our compounds less prone to resistance, we utilize structural bioinformatics to find protein targets from discrete pathways that share similar structural and chemical landscapes in their active-sites. Using structure-based-drug-design we exploit these similarities in active-site architecture to develop inhibitors that simultaneously target proteins from both pathways. To defeat an antibiotic that inhibits two protein targets, the bacteria must mutate two genes instead of just one. A key benefit of this dual target approach is that it dramatically reduces the probability of new strains emerging that are resistant to the new class. Other benefits are expanded spectrum and increased potency.