Chemistry Department Seminar Isaac Krauss Brandeis University"Combining Organic Synthesis and Directed Evolution to Design HIV Vaccine Candidates".
- 5/2/2014 |
3:00 PM – 4:00 PM
Location: Druckenmiller Hall, Room 020
Event Type: Seminar
The Krauss lab is involved in development of novel organic reactions, as well as the application of organic chemistry to HIV vaccine development and chemical glycobiology. To begin this seminar, we will discuss the development of cyclopropanated allylation reagents which exhibit homoallylation activity. Reacting through Zimmerman-Traxler transition states, these reagents selectively afford stereochemical patterns not easily accessed by other methods.
In the second part, we will describe a new method for design of carbohydrate HIV vaccines, which combines organic synthesis and directed evolution techniques. This work originates from the observation that some HIV positive individuals produce antibodies which are broadly neutralizing and protective against HIV infection. One such antibody, 2G12, recognizes and binds to a cluster of carbohydrates on the viral envelope protein gp120. Our goal is to develop synthetic carbohydrate clusters which closely mimic the viral carbohydrate cluster, and which might thus elicit a 2G12-like antibody response when used as a vaccine. In order to design carbohydrate clusters which closely mimic gp120, we have developed evolution-based strategies, in which immobilized 2G12 is used to recognize and fish out the best glycocluster mimics of gp120 from amongst large libraries of ~10 trillion different glycosylated peptide- or DNA structures. The glycocluster structures obtained by these methods are recognized by antibody 2G12 as strongly as is the viral protein itself, and are thus of great interest for vaccine studies.