Abstract
This thesis discusses the synthesis and characterization of four sialic acid-conjugated poly(amidoamine) glycodendrimers as potential inhibitors of the V3 loop of the HIV virus. Known to inhibit the HIV virus by binding to the V3 loop of gp120 are the carbohydrates heparin sulfate (HS) and dextrin sulfate (DS). Unfortunately, HS and DS are also commonly used as anticoagulants and blood thinning agents. Sulfated colominc acid, an α-2, 8 linked homopolymer of sialic acid, is also known to have anti HIV properties without the negative side effects of HS and DS. The drawback to using carbohydrates is that the body will quickly break them down. This leaves little time for the carbohydrates to reach their intended destination. Therefore, a vehicle is necessary to transport the carbohydrates to their site of action before they can be degraded by the body. Dendrimers can meet this need. Dendrimers are large, spherical, macromolecules, whose surface can be functionalized with any sort of molecule including carbohydrates. They have been used for a variety of applications, including medical uses, and are known to be of low toxicity. In addition, dendrimers are multivalent, which means that there are multiple functional groups available to bind either concurrently, or in tandem to a ligand, increasing the overall binding strength of the parent molecule. The work presented in this thesis looks at numerous aspects of dendrimers and their synthesis. In building a dendrimer, there are two possible synthetic routes, convergent and divergent. A convergent synthesis involves building from the outside inward, while a divergent synthesis builds from the inside outward. This work utilized both routes to test which method provided better yields and simplified purifications. In addition to testing the synthetic strategies, two sets of glycodendrimers were made that differed by the addition of a linker between the poly(amidoamine) and the sialic acid. This will allow future work to use these two sets of glycodendrimers to test the effect of dendridic radii on binding strengths. Finally, the synthetic strategy involving all carbohydrates eschewed protecting group chemistry to increase yields and reduce steps. Each additional step takes time and materials, and every reaction risks losing yield. This led to increased yields and decrease synthesis times.