Our lab studies interesting problems in organic synthesis and chemical biology. Our chemical biology program is directed at the design and synthesis of carbohydrate clusters which mimic important binding surfaces in biology. One target is the portion of HIV protein gp120 which is bound by 2G12, a broadly-neutralizing antibody which protects against the virus. Good mimics of this glycocluster have potential as HIV vaccines. Rather than design and test individual glycoclusters, we are using a directed evolution-based approach, in which the best gp120 mimics are selected from a diverse glycocluster library by their ability to bind 2G12. This directed evolution is accomplished by attachment of sugars to a library of DNA sequences using click chemistry, a technique which we term SELMA (SELection with Modified Aptamers). We are also applying SELMA and related methods to other problems in molecular recognition.
Our organic synthesis program is focused on study of mechanistically-interesting reactions which enable access to structural motifs that are difficult to access by other methods. One example is homoallylation reactions. Although a great number of allylation methods are known, known methods for synthesis of the one-carbon homologs are very limited, despite their utility as precursors of stereodefined tetrahydrofurans and tetrahydropyrans. In addition to development of these methods, we are also interested in their application to synthesis of interesting target structures.