Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery
Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 2000.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2005
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| Online Access: | http://hdl.handle.net/1721.1/9384 |
| _version_ | 1811097906052071424 |
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| author | Eckert, Debra M. (Debra Muir), 1973- |
| author2 | Peter S. Kim. |
| author_facet | Peter S. Kim. Eckert, Debra M. (Debra Muir), 1973- |
| author_sort | Eckert, Debra M. (Debra Muir), 1973- |
| collection | MIT |
| description | Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 2000. |
| first_indexed | 2024-09-23T17:06:31Z |
| format | Thesis |
| id | mit-1721.1/9384 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T17:06:31Z |
| publishDate | 2005 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/93842019-04-10T10:29:27Z Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery Eckert, Debra M. (Debra Muir), 1973- Peter S. Kim. Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Dept. of Biology. Biology. Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 2000. Includes bibliographical references. In order to reproduce, enveloped viruses must deposit their genomes into host cells. The first step of this process is the fusion of viral and cellular membranes, which allows the release of the viral contents into the cell. An envelope glycoprotein on the surface of the virus is responsible for fusion. It is usually composed of two subunits, a surface subunit that attaches the virus to the host cell, and a transmembrane subunit that mediates the fusion process. Recent biochemical and structural studies on the transmembrane subunit of the HIV- I virus, gp4 l, have revealed a transient intermediate of the fusion process that is a potential target for anti-viral therapy. After virion attachment to the cell, gp41 undergoes a conformational change and inserts into the target cell membrane. Concomitantly, a conserved region of gp4 l that is hidden both before and after this stage is accessible. The exposed core contains a trimeric coiled coil. A hydrophobic pocket on the surface of this coiled coil has been previously identified as a promising drug target. However, synthetic peptides corresponding to this region aggregate, and are therefore not useful for drug screens. This thesis describes the development of a hybrid molecule that accurately presents the gp41 transient pocket and the use of this hybrid in a screen for potential anti-HIV molecules (Chapter 2 and Chapter 3). Extensive biochemical and structural studies on other viral envelope glycoproteins imply that many diverse viruses utilize similar mechanisms of viral entry (reviewed in Chapter 4 ). Thus, the methods described for targeting the transient intermediate of gp4 l-mediated fusion should be useful for combating many diverse viruses. by Debra M. Eckert. Ph.D. 2005-08-22T20:46:04Z 2005-08-22T20:46:04Z 2000 2000 Thesis http://hdl.handle.net/1721.1/9384 44947893 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 154, [1] leaves 10516958 bytes 10516715 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Eckert, Debra M. (Debra Muir), 1973- Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| title | Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| title_full | Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| title_fullStr | Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| title_full_unstemmed | Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| title_short | Inhibiting HIV-1 entry : utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| title_sort | inhibiting hiv 1 entry utilizing a transient intermediate of viral membrane fusion as a target for drug discovery |
| topic | Biology. |
| url | http://hdl.handle.net/1721.1/9384 |
| work_keys_str_mv | AT eckertdebramdebramuir1973 inhibitinghiv1entryutilizingatransientintermediateofviralmembranefusionasatargetfordrugdiscovery |