U.S.-Japan Cooperative Research: Catalytic Antibodies

该奖项将支持宾夕法尼亚州立大学化学系的Stephen Benkovic教授和日本北海道大学的Eiko Ohtsuka教授进行的为期两年的合作研究项目。合作的目标是开发催化抗体，促进RNA结构中的酰胺合成和磷二酸酯的酯交换。这项研究将利用这一领域的两个最新科学进展，即(1)产生类似于给定反应的过渡态的抗体，这种抗体以相当快的速度和极高的特异性催化化学键的合成或断裂；(2)证明这种单抗可以在细菌中构建。这些进展为构建由数百万个Fab片段组成的文库开辟了道路，该文库经过结合筛选和催化活性测试。此外，现在可以使用发酵在具有成本效益的基础上生产所需的克量抗体。作为这项研究的结果，人们希望开发出有助于理解核酶、RNA裂解酶的作用方式的催化剂，以及开发构建酰胺键的更好方法，以加速激素活性多肽的合成。两位合作的研究人员都是非常有能力的科学家，取得了杰出的成就，每个人都被认为是各自领域的专家。他们的长处是互补的；本科维奇教授将专注于催化机理，大冢教授将专注于2D核磁共振的结构性质。这一领域的任何进展都将带来重大的科学和工业利益。如果这个项目成功，它应该会对现代生物学产生重大影响。

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.