Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2006
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| Online Access: | http://hdl.handle.net/1721.1/32429 |
| _version_ | 1811085479398866944 |
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| author | Rothman, Deborah Maria |
| author2 | Barbara Imperiali. |
| author_facet | Barbara Imperiali. Rothman, Deborah Maria |
| author_sort | Rothman, Deborah Maria |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. |
| first_indexed | 2024-09-23T13:10:15Z |
| format | Thesis |
| id | mit-1721.1/32429 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T13:10:15Z |
| publishDate | 2006 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/324292019-04-12T14:30:54Z Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways Rothman, Deborah Maria Barbara Imperiali. Massachusetts Institute of Technology. Dept. of Chemistry. Massachusetts Institute of Technology. Dept. of Chemistry. Chemistry. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. Vita. Includes bibliographical references. Within cellular signaling, protein phosphorylation is the post-translational modification most frequently used to regulate protein activity. Protein kinases and phosphoprotein phosphatases generate and terminate these phosphoryl signals, respectively. Chemical approaches for studying protein phosphorylation and the roles of phosphoproteins include photolabile caged analogs of bioactive species. Caged compounds are ideal chemical probes for studying cellular signaling because they afford researchers spatial and temporal control over the release of targeted effector molecules. Ligands or proteins involved in signal transduction can be chemically caged and subsequently irradiated to release a concentration burst of a specific species, allowing the downstream effects to be monitored without disrupting other aspects of the system. The syntheses and applications of caged phosphopeptides and phosphoproteins have been developed and detailed within this thesis. Two methods to synthesize 1-(2-nitrophenyl)ethyl caged phosphopeptides were developed. These peptides demonstrated good quantum yields of uncaging as compared to literature values of other ortho-nitrobenzyl derived caged compounds. A study in which these caged phosphopeptide tools yielded seminal information about the 14-3-3 protein family's involvement in cell cycle control successfully demonstrated the unique utility of these probes. Furthermore, the synthesis that allowed the extension of the nonsense codon suppression methodology to include caged phosphoproteins was developed. (cont.) The three most commonly phosphorylated amino acids (serine, threonine, and tyrosine) were each incorporated into a test protein in their caged phosphorylated form. Toward studying cell motility, caged phosphoserine was incorporated into position 153 of mVASP for use in live cell assays. by Deborah Maria Rothman. Ph.D. 2006-03-29T18:43:51Z 2006-03-29T18:43:51Z 2005 2005 Thesis http://hdl.handle.net/1721.1/32429 61717950 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 161, [2] leaves 8859555 bytes 8868658 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Chemistry. Rothman, Deborah Maria Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways |
| title | Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways |
| title_full | Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways |
| title_fullStr | Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways |
| title_full_unstemmed | Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways |
| title_short | Caged phosphopeptides and phosphoproteins : agents in unraveling complex biological pathways |
| title_sort | caged phosphopeptides and phosphoproteins agents in unraveling complex biological pathways |
| topic | Chemistry. |
| url | http://hdl.handle.net/1721.1/32429 |
| work_keys_str_mv | AT rothmandeborahmaria cagedphosphopeptidesandphosphoproteinsagentsinunravelingcomplexbiologicalpathways |