News and Publications
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
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.