The synthesis of an HIV carbohydrate epitope vaccine is proposed. The vaccine design is based upon recent crystallographic information about the binding interactions of human antibody 2G12 with the oligosaccharides found on the surface of the HIV protein gp120. The findings in this study suggest that the strong 2G12-gp120 binding is made possible by the cooperativity of a multivalent interaction between 2G12 and a cluster of several glycans. The vaccine synthesized in this laboratory will seek to mimic this spatial presentation of two or more glycans to form a similar cluster. After the initial design has been synthesized, the vaccine will then be tested in collaboration with biologists, to see whether it stimulates the production of 2G12-like antibodies, capable of neutralizing a broad range of HIV-1 isolates. Based on the results of these studies, the vaccine will be redesigned, resynthesized and retested. Many cycles of this process will hopefully teach us a great deal about vaccines, HIV, and organic synthesis.
| Krauss, Isaac J; Joyce, Joseph G; Finnefrock, Adam C et al. (2007) Fully synthetic carbohydrate HIV antigens designed on the logic of the 2G12 antibody. J Am Chem Soc 129:11042-4 |
| Krauss, Isaac J; Mandal, Mihirbaran; Danishefsky, Samuel J (2007) Total synthesis of (+)-isomigrastatin. Angew Chem Int Ed Engl 46:5576-9 |
