QUALITY CONTROL OF STUDIES OF OLIGOSACCHARIDE CHEMICAL ENZYMATIC SYNTHESIS

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Oligosaccharides that block the adherence of bacteria to epithelial cells in vitro-lacto-N-neotetraose (LNnT) and its alpha 2-1,3- and alpha 2-6-sialylated derivatives were tested for their abilities to attenuate the course of pneumococcal pneumonia and to prevent colonization of thenasopharynx in animal models. Intratracheal administration of these agents concurrently with bacteria dramatically decreased pneumococcal load in the lungs of rabbits and conferred protection from bacteremia. Several oligosaccharides were prepared by a combination of chemical andenzymatic synthesis. The samples ameliorated pneumonia and bacteremia when given therapeutically 24 h after infection was established. When administered intranasally, neoglycoconjugates of the active oligosaccharides prevented colonization of the nasopharynx of infant rats. In addition to in-vitro anti-adherence properties, LNnT acted directly on cultured lung epithelial cell lines to induce changes such that pneumococcal adherence was prevented for prolonged periods. These activities have encourage continued development of oligosaccharides as a class of potentially preventive and therapeutic agents for infectious diseases. The work with the MS Resource is to carefully check the products synthesized for sequence and linkage. Additional concern for the compounds prepared is that we have some assessment for purity.