{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/31289"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/31289","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"Thioamides And Proteolysis: Examining The Effects And Applications Of A Single-Atom Substitution","abstract":"Thioamide substitution in the peptide backbone enables several applications in studying proteolysis, monitoring protease activity and in selective protease inhibition. To date, we have used model substrates to investigate the positional effects that these thioamide substitutions have on proteolysis rates, as well to examnine the ability of thioamides to stabilize peptides for imaging applications. In order to determine the positional effects of thioamides, we have examined several model peptides with a thioamide scanned from the P3 position to the P3' position and identified thioamide perturbing and non-perturbing positions. Further mechanistic investigation showed that the primary effect of the thioamide is often to prevent binding to the protease. Finally, incorporation of a thioamide into a peptide scaffold that is known to selectively bind to the neuropeptide Y Y1 receptor increased its serum stability, without affecting its affinity for the receptor. Currently, we are optimizing this stabilized imaging peptide usage in animals by changing linkers, fluorophores, and N-terminal modifications. We are also developing a system where full-length peptide hormones can be expressed, stabilized via thioamidation, and tagged with a fluorophore to afford in vivo peptide hormone imaging agents. Together, these studies provide guidelines for positioning thioamides for various proteolysis applications and show that thioamides can be used to create stabilized imaging peptides.","abstract_html":"Thioamide substitution in the peptide backbone enables several applications in studying proteolysis, monitoring protease activity and in selective protease inhibition. To date, we have used model substrates to investigate the positional effects that these thioamide substitutions have on proteolysis rates, as well to examnine the ability of thioamides to stabilize peptides for imaging applications. In order to determine the positional effects of thioamides, we have examined several model peptides with a thioamide scanned from the P3 position to the P3' position and identified thioamide perturbing and non-perturbing positions. Further mechanistic investigation showed that the primary effect of the thioamide is often to prevent binding to the protease. Finally, incorporation of a thioamide into a peptide scaffold that is known to selectively bind to the neuropeptide Y Y1 receptor increased its serum stability, without affecting its affinity for the receptor. Currently, we are optimizing this stabilized imaging peptide usage in animals by changing linkers, fluorophores, and N-terminal modifications. We are also developing a system where full-length peptide hormones can be expressed, stabilized via thioamidation, and tagged with a fluorophore to afford in vivo peptide hormone imaging agents. Together, these studies provide guidelines for positioning thioamides for various proteolysis applications and show that thioamides can be used to create stabilized imaging peptides.","abstract_has_math":false,"creators":["Barrett, Taylor Mallory"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Ernest J. 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To date, we have used model substrates to investigate the positional effects that these thioamide substitutions have on proteolysis rates, as well to examnine the ability of thioamides to stabilize peptides for imaging applications. In order to determine the positional effects of thioamides, we have examined several model peptides with a thioamide scanned from the P3 position to the P3' position and identified thioamide perturbing and non-perturbing positions. Further mechanistic investigation showed that the primary effect of the thioamide is often to prevent binding to the protease. Finally, incorporation of a thioamide into a peptide scaffold that is known to selectively bind to the neuropeptide Y Y1 receptor increased its serum stability, without affecting its affinity for the receptor. Currently, we are optimizing this stabilized imaging peptide usage in animals by changing linkers, fluorophores, and N-terminal modifications. We are also developing a system where full-length peptide hormones can be expressed, stabilized via thioamidation, and tagged with a fluorophore to afford in vivo peptide hormone imaging agents. Together, these studies provide guidelines for positioning thioamides for various proteolysis applications and show that thioamides can be used to create stabilized imaging peptides."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Thioamides And Proteolysis: Examining The Effects And Applications Of A Single-Atom Substitution"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ernest J. Petersson"],"dc:creator":["Barrett, Taylor Mallory"],"dc:date":["2023-05-18T01:19:02.000"],"dc:date.accessioned":["2023-05-22T18:06:16Z"],"dc:date.available":["2001-01-01T00:00:00Z"],"dc:date.issued":["2020"],"dc:description.abstract":["Thioamide substitution in the peptide backbone enables several applications in studying proteolysis, monitoring protease activity and in selective protease inhibition. To date, we have used model substrates to investigate the positional effects that these thioamide substitutions have on proteolysis rates, as well to examnine the ability of thioamides to stabilize peptides for imaging applications. In order to determine the positional effects of thioamides, we have examined several model peptides with a thioamide scanned from the P3 position to the P3' position and identified thioamide perturbing and non-perturbing positions. Further mechanistic investigation showed that the primary effect of the thioamide is often to prevent binding to the protease. Finally, incorporation of a thioamide into a peptide scaffold that is known to selectively bind to the neuropeptide Y Y1 receptor increased its serum stability, without affecting its affinity for the receptor. Currently, we are optimizing this stabilized imaging peptide usage in animals by changing linkers, fluorophores, and N-terminal modifications. We are also developing a system where full-length peptide hormones can be expressed, stabilized via thioamidation, and tagged with a fluorophore to afford in vivo peptide hormone imaging agents. Together, these studies provide guidelines for positioning thioamides for various proteolysis applications and show that thioamides can be used to create stabilized imaging peptides."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/31289"],"dc:language":["en"],"dc:rights":["Taylor Mallory Barrett"],"dc:title":["Thioamides And Proteolysis: Examining The Effects And Applications Of A Single-Atom Substitution"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:47:06Z"}