Author : Theodore Michael Tarasow
Publisher :
ISBN 13 :
Total Pages : 278 pages
Book Rating : 4.:/5 (763 download)
Book Synopsis Tailored Biocatalysts for Carbon-carbon Bond Forming and Cleaving Reactions by : Theodore Michael Tarasow
Download or read book Tailored Biocatalysts for Carbon-carbon Bond Forming and Cleaving Reactions written by Theodore Michael Tarasow and published by . This book was released on 1994 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt: Carbon-carbon bond forming and cleaving reactions represent some of the most useful and fascinating of all chemical transformations. The mechanism and scope of many of these reactions have been rigorously studied not only because of their intrinsic chemical interest but also because carbon-carbon bond forming and cleaving transformations play essential roles in both biological (enzymatic transformations) and nonbiological processes (organic synthesis). My doctoral research has involved three areas related to the catalysis of carbon-carbon bond forming and cleaving reactions. Specifically, my work has built on previous achievements in this area, focusing on the investigation of factors important in antibody catalysis, the expansion of the current antibody-catalyzed reaction repertoire, and the extension of the transition state analog approach for generating catalysts to new macromolecular receptors. Thus, I have characterized a family of decarboxylase antibodies raised against the same naphthalene disulfonate hapten in order to gain some insights into medium effects in protein catalysis. A general, parallel trend in binding site hydrophobicity and catalytic efficiency was apparent, but the few inconsistencies observed emphasized the fact that proteins can solve catalytic challenges in a number of ways, regardless of how simple the model reaction seems. I have also applied TRNOE techniques for the first time to a catalytic antibody system to investigate the bound conformation of a flexible substrate molecule. These studies show that binding site properties correlate to a certain extent with hapten design, and that antibodies generated against a compact transition state analog can use their binding energy to fix substrate in a high energy conformation resembling the hapten. Research toward expanding the reaction repertoire of catalytic antibodies has involved designing and synthesizing transition state analogs for a tandem aza-Cope-Mannich reaction and for an industrially relevant Diels-Alder reaction. The fact that no catalysts were detected in either experiment points out our incomplete knowledge of effective hapten design. Finally, I have applied in vitro selection techniques to isolate RNA molecules capable of binding a Diels-Alder cycloaddition transition state analog. These unique receptors were assayed for their ability to catalyze the cognate Diels-Alder reaction using a newly developed catELISA technique. While a novel ribozyme was not isolated, the results provide a foundation from which to further pursue RNA catalysis.