The total synthesis of furanomycin and studies towards its incorporation into human hemoglobin /
There is considerable interest in incorporating unnatural amino acids into proteins. Though considerable progress has been made toward achieving this end, there is still much work to be done. We are interested in adding to those translatable amino acid analogs the natural product furanomycin. Fur...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2001.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=725912361&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | There is considerable interest in incorporating unnatural amino acids into proteins. Though considerable progress has been made toward achieving this end, there is still much work to be done. We are interested in adding to those translatable amino acid analogs the natural product furanomycin. Furanomycin is known to have in vitro translational activity, but this property has yet to be exploited in an in vivo expression system. In order to study the in vivo translational activity of furanomycin effectively, we required significant amounts of the natural product. To achieve this end we developed a synthesis of furanomycin that would enable us to produce muti-milligram quantities of furanomycin and related analogs quickly. Our synthesis utilizes a silver nitrate catalyzed cyclization of an allenic alcohol as the key step to access the dihydrofuran core of furanomycin quickly. The requisite allenic alcohol was easily constructed via reduction of a mono-protected propargylic diol. The propargylic diol was constructed by a simple addition to a serinal derivative, Garner aldehyde. Efforts then focused on incorporating furanomycin into a protein, human hemoglobin. Our work required the introduction of an isoleucine codon into a hemoglobin expression plasmid, which after considerable effort was successfully accomplished. This enabled us to explore the in vivo substitution of furanomycin for isoleucine in hemoglobin. initial efforts were unable to produce a hemoglobin containing furanomycin. However, significant progress was made towards the expression and purification of the protein. Moreover, a better understanding of the biological mechanism of furanomycin was achieved, which should allow further studies to progress more fruitfully. |
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| Item Description: | Vita. "Major Subject: Chemistry". |
| Physical Description: | xix, 151 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 118-123). |