Studies of oxygen-containing organic compounds

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This application is divided into three areas all of which involve oxygen-containing organic compounds.  The first of these deals with the interactions of cell surface carbohydrates with proteins.  Cell surfaces are covered by carbohydrate chains that are involved in recognition of proteins through interactions that are normally weak.  One medically significant example is the attachment of the uropathegenic bacteria E. coli to the surface of the intestinal tract which takes place through binding of protein on threads projecting from the bacterial surface to carbohydrates on the tissue surface.  It is proposed to synthesize two classes of large molecules (dendrimers), including one new class, that are able to present multiple copies of the sugar that will interfere with this binding.  Another example of interest is the protein DC-SIGN present on certain human tissues, that is thought to be involved in bringing a variety of pathogens into the body including viruses (HIV, hepatitis C), bacteria, yeasts and parasites.  Binding to surface carbohydrates on the pathogen is the initial step in this process that could be disrupted by competing binding agents, such as variants on the dendrimers proposed above having appropriate geometries.  A second area involves the synthesis of the repeating unit of the common antigen of all Streptococcus pneumoniae serotypes, the C-polysaccharide, segments of this repeating unit, and oligomers of the repeating unit.  Larger compounds in which these compounds are attached to dendrimers and/or proteins will be evaluated as vaccines.  A third part of the application contains a proposal to continue the investigation of several aspects of the very useful stannylene reaction both computationally and experimentally in order to understand why it gives regioselective reactions.  This improved understanding should lead to the synthesis of alternative dialkyltin alkoxides that give improved and more controlled regioselectivity in substitution of diols and polyols which would be generally useful for the synthesis of substituted carbohydrates and other compounds containing multiple hydroxyl groups.