Design and Synthesis of Potential Cell Division Modulators

FtsZ is a highly conserved bacterial cell division protein, making it a novel target for the development of small molecules that can act as cell division modulators. The N- and C-terminus of this protein are connected by helix 7. The C-terminus of FtsZ contains the T7 loop, this loop activates the GTPase activity by making contact with the N-terminus (the nucleotide site) of another FtsZ monomer. In addition, the T7 loop of FtsZ is also the site where SulA, an endogenous inhibitor of FtsZ, binds. During the SOS response, the process that triggers DNA repair, SulA causes cell filamentation by preventing the polymerization of FtsZ that leads to cell division. Mimicking the functions of the T7 loop of FtsZ, will help in the rational design of small molecules that can be used in conjunction with antibiotics for the treatment of bacterial infections. Our central hypothesis is that by synthesizing mimics of the T7 loop region of FtsZ we will gain valuable information that will lead to the discovery of small molecules that can act as bacterial cell division modulators.