Brent L. Iverson
Catalytic AntibodiesCatalytic antibodies are an exciting new class of catalysts that offer catalytic activity combined with exquisite programmable specificity. For example, catalytic antibodies have been produced that exhibit precise substrate specificity, regioselectivity and stereoselectivity reminiscent of natural enzymes. Our group is pioneering the use of polyclonal antibodies in the development of better catalytic antibodies for both synthetic organic chemistry and therapeutic applications. (D.B. Stephens and B.L. Iverson, Biochem. Biophys. Res. Commun, 1993, 192, 1439-1444. "Catalytic Polyclonal Antibodies.") Our polyclonal antibody approach is twice as fast and more than ten-fold less costly then currently used methods. Best of all, the results obtained with polyclonal antibodies are of more general value, so we can more accurately identify important trends through systematic comparative studies. A student working with catalytic antibodies will become proficient in a wide range of important techniques including computer assisted molecular design, synthetic organic chemistry, immunological techniques, protein purification and catalytic assays. Such a student will possess a broad understanding of bioorganic chemistry, providing a solid foundation for a career in the biotechnology industry, the pharmaceutical industry or academic chemistry.
In a related project, our group is collaborating with the group of Dr. George Georgiou in the Department of Chemical Engineering in order to create a new system capable of producing important antibody molecules using only bacteria, not immunized animals. Our approach utilizes libraries of antibody fragments (single chain Fv fragments as shown above) attached to the surface of E. coli bacteria and selection of desirable antibodies using fluorescence-activated cell sorting (FACS). (J.A. Francisco, R. Campbell, B.L. Iverson and G. Georgiou, Proc. Nat. Acad. Sci.,1993, 90, 10444-10448. "Production and Fluorescence-Activated Cell Sorting of Escherichia coli Expressing a Functional Antibody Fragment on the External Surface.") We will use our new system to create even better catalytic antibodies that cannot be made using animal immunization techniques. A student working on this project will become proficient in many important areas of molecular biology relevant to the biotechnology industry or academic research including PCR, generation of molecular diversity, FACS, protein expression and large scale production of recombinant proteins.
In collaboration with the Sessler group of this department, we are elucidating and attempting to exploit a novel interaction we have discovered between a class of expanded porphyrin molecules called sapphyrins and nucleic acids. ( B.L. Iverson, K. Shreder, V. Kral and J.L. Sessler, J. Am. Chem. Soc., 1993, 115, 11022-11023. "Phosphate Recognition by Sapphyrin. A New Approach to DNA Binding.") Current projects include production of a chromatographic support for the separation of phosphate-containing molecules, as well as further investigation of the details of sapphyrin-nucleic acid interactions. A student working on this project will acquire expertise in computer-assisted molecular design, synthetic chemistry, small-molecule nucleic acid interactions, and numerous spectroscopic methods important for a career in the pharmaceutical industry or academic chemistry.