Eric V. Anslyn
Department of Chemistry and Biochemistry
University of Texas, Austin
Austin, TX 78712
1991 Searle Scholar
My research group is interested in the physical and bioorganic chemistry of synthetic and natural receptors and catalysts. Using a combination of synthesis, NMR, slow and fast kinetics, electrochemistry, and computer modeling, we design and implement studies oriented at the development of compounds which perform certain aims and tasks. In specific, we focus upon catalysts of phosphoryl and glycosyl transfers, and receptors for carbohydrates and enolates. In addition, we seek to form polymeric molecules that exhibit unique abiotic secondary structure and are useful in novel combinatorial library applications.
In the arena of phosphoryl transfer, the work involves investigation of the cooperativity of guanidiniums, metals and general bases. These functional groups are common elements of natural phosphatases. We make simple synthetic analogs of the natural systems. For example, compound 1 (see figure) has been found to bind and enhance the imidazole catalyzed hydrolysis of RNA. We are currently incorporating general bases and electrophilic metals into the structure of 1 as a means of producing a multifunctional RNA cleaving artificial enzyme.
Another direction for catalysis we are pursuing involves the alkylation of
enolates. We have studied the binding properties of enolates of active methylene
compounds to structures such as 2 (see figure).
Catalysis of enolate alkylation can arise with such systems by a modulation of the enolates pKa's upon complexation. Proper pKa shifts can induce enolate formation and alkylation only in the presence of the catalyst. Currently, chiral versions of these catalysts are being formed as a means of achieving catalytic asymmetric alkylations.
As another example of developing receptors, compound 3 is being investigated as an electrochemical sensor of glucose concentrations in blood. The design of this receptor features two boronic acid moieties which reversibly form boronic esters with glucose in aqueous media. Upon complexation of the sugar, the oxidation potential of Cu+ is changed, and thus deposition of 3 on an electrode yields a sensor in which following the current at the oxidation potential gives the glucose concentration.
Finally, as a means of developing receptors and catalysts, we are pursuing the formation of combinatorial libraries of non-peptidic polymers. In specific, we are developing solid phase synthesis methods for polythioureas 4. The goal is the formation of libraries of these novel polymers, from which useful receptors can be isolated by various screening methods. This is a new area of research for our group, but in a similar manner to our other projects, it nicely combines synthetic and molecular biology approaches to achieving practical results.
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