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The Skaggs Institute for Chemical Biology
Scientific Report 1999-2000


Organic Chemistry With Biological Molecules


M.G. Finn, M. Dintzner, Q. Wang

We seek to uncover and use the unique patterns of reactivity of transition metals in a multidisciplinary approach for the development of new reagents, catalysts, and synthetic processes.

Catalytic Antibodies: Reactive Immunization and Metal-Based Reactivity

In collaboration with R.A. Lerner and C.F. Barbas, the Skaggs Institute, we are enlarging the scope of enantioselective reactions that can be performed by catalytic antibody systems. The strong association of ß-diketones with the active sites of aldolase antibodies enables us to import nonbiological reactivity engines into the chiral binding pockets on the backs of diketones. We are attempting this step with several metal complexes that are catalysts for important oxidation reactions. Using phage display, we can also evolve antibodies with binding pockets specifically engineered for this role as catalyst "host."

The technique of reactive immunization, developed by R.A. Lerner and coworkers at The Scripps Research Institute, is a powerful method for eliciting catalytic function. New reactive haptens have been developed for this purpose, such as the electrophiles shown in Figure 1. Immunization with these systems is now under way to probe the limits of what is necessary for the evolution of aldolase activity as a function of hapten structure and reactivity. A spin-off of this work was the discovery of a new amine-catalyzed synthesis of 2H-chromenes (Fig. 2).

Virus-Based Reagents, Catalysts, and Materials

The structures and molecular biology of many plant and bacterial viruses are now sufficiently well understood so that the viruses are attractive systems for chemists to use in the rational design of agents with new properties and functions. In collaboration with J. Johnson and coworkers, The Scripps Research Institute, we are using cowpea mosaic virus as a prototype for such efforts. Our goals are to use the virus as a chemical reagent for the construction of materials and as a platform for the support of chemical catalysts. Site-directed mutagenesis is under way to place reactive groups at designed positions of the viral capsid, and investigations into the fundamental aspects of viral infectivity are also in progress. With this work, we hope to bring to the world of chemistry well-defined building blocks of unusual size (20-60 nm) and molecular mass (millions of daltons).

Publications

Hall, I.H., Tolmie, C.E., Barnes, B.J., Curtis, M.A., Russell, J.M., Finn, M.G., Grimes, R.N. Cytotoxicity of tantalum(V) and niobium(V) small carborane complexes and mode of action in P388 lymphocytic leukemia cells. Appl. Organometal. Chem. 14:108, 2000.

Maddock, S.M., Finn, M.G. Palladium-catalyzed head-to-head telomerization of isoprene with amines. Organometallics, in press.

 

 







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