Abstract
The human immunodeficiency virus (HIV) affects people around the globe. According to the National Institutes of Health, around 33.3 million individuals worldwide are infected with HIV-1, and within this group more than 1 million people are found in the United States. There are therapeutic treatments used to fight HIV before it develops into AIDS (acquired immunodeficiency syndrome), but they are not without drawbacks. Viral resistance and harmful side effects are problems that have led to new research directed towards fighting this virus. Most of the drugs created thus far attack the virus from within the host cell. Scientists are now looking at targets on the viral surface that would prevent the virus from entering the cell. Dendrimers, which have been around since the mid 1980s, have the potential to block viral entry through the multivalent effect. Dendrimers are branched macromolecules that are globular in shape, and structurally well-defined with multivalent reactive terminal groups. As these molecules branch out from the core, new generations of compounds may be added to double the number of reactive ends. When the end groups on a dendrimer are carbohydrates, it is known as a glycodendrimer. There are two processes used to formulate glycodendrimers called the divergent and convergent methods. In the divergent method, dendrimers are synthesized from the core outwards. With the convergent technique, the outer portions are synthesized first and then added to the core. Dendrimers have been utilized in a variety of ways since their creation in 1984. In some studies, glycodendrimers have demonstrated anti-HIV properties. The goal in this research was to create two glycodendrimers using both the convergent and divergent processes. The hexavalent maltose amino-oxime glycodendrimer was synthesized (66% yield) using the convergent method and the trivalent maltose amino-amide glycodendrimer was created (3.4% yield) via the divergent method. A hexavalent amino core (16% yield) was synthesized as well, which will be used in later research to create other glycodendrimers. In the end, once these glycodendrimers are sulfated, they will be evaluated in a competitive gp120 binding assays for binding affinity. If strong affinity between gp120 and the glycodendrimers is established, then these glycodendrimers will be further assessed in an inhibition of viral infectivity assay. This assay will involve HIV in vitro with active viral particles. In the end, this research could lead to the prevention of HIV infection.