This award will support a two year cooperative research project involving Professor Stephen Benkovic, Department of Chemistry, Pennsylvania State University, and Professor Eiko Ohtsuka, Hokkaido University, Japan. The objective of the collaboration is to develop catalytic antibodies that promote amide synthesis and transesterification of phosphodi- esters in RNA structures. This research will exploit two recent scientific advances in this area, namely (1) the production of antibodies that resemble the transition state of a given reaction which catalyze the synthesis or breakage of chemical bonds with substantial rate accelerations and with exquisite specificity; and (2) the demonstration that such monoclonal antibodies can be constructed in bacteria. These advances open the way for constructing a library consisting of several million FAB fragments, screened for binding and tested for catalytic activity. Additionally, the production of gram quantities of a desired antibody can now be carried out on a cost efficient basis using fermentation. It is hoped, as a result of this research, to develop catalysts which will be useful in understanding the mode of action of ribozymes, the RNA cleaving enzymes, as well as developing superior means of constructing amide bonds expediting the synthesis of hormonally active peptides. Both collaborating researchers are highly competent scientists with distinguished accomplishments, and each is considered an expert in his individual field. Their strengths are compleme- ntary; Professor Benkovic will concentrate on the mechanism of catalysis and Professor Ohtsuka on the structural properties of 2D NMR. Any advances in this area will have significant benefits, both scientific and industrial. If this project is successful it should have a major impact on modern biology.
