SIALIDASE INHIBITORS TO PREVENT BACTERIAL VAGINOSIS RELATED PREMATURITY. J. Tsao, C. White, M. Luo, Center for Macromolecular Crystallography, University of Alabama in Birmingham, Birmingham, AL.35294

Bacterial vaginosis (BV) is one of the common vaginal infectious disorder affecting women of reproductive ages, including 15-20% of pregnant women. Many studies have indicated the link between BV and prematurity, but the pathophysiological mechanism are still poorly understood. However, elevated sialidase activity is directly correlated with the prematurity outcomes of pregnant BV patients. In many bacteria infections, bacteria sialidases play an important roles in host cell adhesion and have been implicated in pathogenicity. We have designed three new classes of bacteria sialidase specific inhibitors based in the active site structure of Salmonella typhimurium LT2 sialidase. The inhibitors were constructed using two benzoic acid-based lead compounds and targeting towards a hydrophobic pocket located near Trp 128 and a strong anionic pocket located between Asp 100 and Glu 231 in the bacterial sialidase active site. Several synthesized inhibitor compounds show measurable inhibition of sialidase activity. We soaked two of the compounds into the Salmonella typhimurium crystals and determined the structure of the complexes. The inhibitors interact with the active site residues through hydrogen binding and hydrophobic interactions. Those complex structures will help to design more effective inhibitors that are specific to the bacterial vaginosis related bacteria sialidase.