Final Abstract for URS Program
Carbohydrates (glycans) form the basis of all living organisms and, consequently, are ubiquitous both in nature as biologically active compounds and in medicine as pharmaceuticals. One important application of carbohydrate-based drugs (glycopharmaceuticals) is the treatment of microbial sepsis, an acute illness that causes 100,000+ human deaths annually in the US alone. Exposure of the patient’s blood system to E. coli bacteria causes a massive, and often fatal, immune response. One important cellular receptor that senses the bacterium and is critically involved in triggering the immune response is CD14. Significant efforts by our team and others have been made to develop carbohydrate-based drugs called anti-microbial antagonists that target and block the CD14 receptor, thus terminating the infection/immune response cascade. Nevertheless, microbial sepsis remains a long-standing, difficult-to-solve problem that requires innovative approaches since progress in this unmet medical need has been difficult to achieve.
Among new promising developments is antagonist AM-12 that is an attractive drug candidate due to its relatively simple structure, stability, potent activity, and lack of toxicity, discovered by Drs. Demchenko and Nichols (UMSL). To capitalize on this discovery of this promising anti-microbial receptor antagonist and extend this development to new therapeutic avenues, my project aims to develop a range of novel carbohydrate-derived drugs. At the completion of this projects, my synthetic compounds with superior pharmaceutical properties will help to accelerate discovery in many scientific disciplines with significant public health impact.