{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10072"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10072","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Development and Application of Chemoenzymatic Tools to Investigate Site-Specific Protein ADP-Ribosylation","abstract":"Herein I have developed the first technologies to install mono- and poly-ADP-ribosylation at specific sites on synthetic peptides and full-length proteins. Historically, chemical and topological complexities associated with ADP-ribosylation have stymied progress in this area. To overcome this, I have identified enzymes capable of: (i) installing ADP-ribose specific side chain functionalities on synthetic peptides, and (ii) elongating ADP-ribose chains from mono-ADP-ribosylated substrate peptides. These enzymes are highly efficient and promiscuous in regard to substrate peptide amino acid sequence. ADP-ribosylated peptides are compatible with N-terminal and C-terminal protein ligation technologies to afford assembly of homogenous, full-length proteins bearing ADP-ribosylation at user-defined sites. These reagents were then employed to address fundamental questions regarding the structure, function, and regulation of different ADP-ribose:protein linkage types and specific ADP-ribosylation sites on chromatin and chromatin associated proteins. Overall, the work discussed here reveals basic chemical and biological principles of arginine, aspartate, glutamate, and serine ADP-ribosylation and enables new strategies to interrogate the biochemical consequences of this widespread protein modification in human physiology and disease.","abstract_html":"Herein I have developed the first technologies to install mono- and poly-ADP-ribosylation at specific sites on synthetic peptides and full-length proteins. Historically, chemical and topological complexities associated with ADP-ribosylation have stymied progress in this area. To overcome this, I have identified enzymes capable of: (i) installing ADP-ribose specific side chain functionalities on synthetic peptides, and (ii) elongating ADP-ribose chains from mono-ADP-ribosylated substrate peptides. These enzymes are highly efficient and promiscuous in regard to substrate peptide amino acid sequence. ADP-ribosylated peptides are compatible with N-terminal and C-terminal protein ligation technologies to afford assembly of homogenous, full-length proteins bearing ADP-ribosylation at user-defined sites. These reagents were then employed to address fundamental questions regarding the structure, function, and regulation of different ADP-ribose:protein linkage types and specific ADP-ribosylation sites on chromatin and chromatin associated proteins. Overall, the work discussed here reveals basic chemical and biological principles of arginine, aspartate, glutamate, and serine ADP-ribosylation and enables new strategies to interrogate the biochemical consequences of this widespread protein modification in human physiology and disease.","abstract_has_math":false,"creators":["Tashiro, Kyuto"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["DeBose-Boyd, Russell A.","Liszczak, Glen","Phillips, Margaret A.","Ready, Joseph M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-06-07T18:16:48Z","date_published":"2023-06-07T18:16:48Z","updated_at":"2026-07-24T05:52:38Z","subjects":["ADP-Ribosylation","Peptides","Serine","Adenosine Diphosphate Ribose"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1381370413"],"render_values":[{"text":"1381370413","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10072","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["DeBose-Boyd, Russell A.","Liszczak, Glen","Phillips, Margaret A.","Ready, Joseph M."]},{"key":"dc:creator","label":"Author","values":["Tashiro, Kyuto"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2023-06-07T18:16:48Z","2023-05","2023-05-01T05:00:00.000Z","May 2023","2023-06-07T18:16:49Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["ADP-Ribosylation","Peptides","Serine","Adenosine Diphosphate Ribose"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10072","1381370413"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Herein I have developed the first technologies to install mono- and poly-ADP-ribosylation at specific sites on synthetic peptides and full-length proteins. Historically, chemical and topological complexities associated with ADP-ribosylation have stymied progress in this area. To overcome this, I have identified enzymes capable of: (i) installing ADP-ribose specific side chain functionalities on synthetic peptides, and (ii) elongating ADP-ribose chains from mono-ADP-ribosylated substrate peptides. These enzymes are highly efficient and promiscuous in regard to substrate peptide amino acid sequence. ADP-ribosylated peptides are compatible with N-terminal and C-terminal protein ligation technologies to afford assembly of homogenous, full-length proteins bearing ADP-ribosylation at user-defined sites. These reagents were then employed to address fundamental questions regarding the structure, function, and regulation of different ADP-ribose:protein linkage types and specific ADP-ribosylation sites on chromatin and chromatin associated proteins. Overall, the work discussed here reveals basic chemical and biological principles of arginine, aspartate, glutamate, and serine ADP-ribosylation and enables new strategies to interrogate the biochemical consequences of this widespread protein modification in human physiology and disease."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Development and Application of Chemoenzymatic Tools to Investigate Site-Specific Protein ADP-Ribosylation"]}]}],"canonical_facts":{"dc:contributor":["DeBose-Boyd, Russell A.","Liszczak, Glen","Phillips, Margaret A.","Ready, Joseph M."],"dc:creator":["Tashiro, Kyuto"],"dc:date":["2023-06-07T18:16:48Z","2023-05","2023-05-01T05:00:00.000Z","May 2023","2023-06-07T18:16:49Z"],"dc:description":["Herein I have developed the first technologies to install mono- and poly-ADP-ribosylation at specific sites on synthetic peptides and full-length proteins. Historically, chemical and topological complexities associated with ADP-ribosylation have stymied progress in this area. To overcome this, I have identified enzymes capable of: (i) installing ADP-ribose specific side chain functionalities on synthetic peptides, and (ii) elongating ADP-ribose chains from mono-ADP-ribosylated substrate peptides. These enzymes are highly efficient and promiscuous in regard to substrate peptide amino acid sequence. ADP-ribosylated peptides are compatible with N-terminal and C-terminal protein ligation technologies to afford assembly of homogenous, full-length proteins bearing ADP-ribosylation at user-defined sites. These reagents were then employed to address fundamental questions regarding the structure, function, and regulation of different ADP-ribose:protein linkage types and specific ADP-ribosylation sites on chromatin and chromatin associated proteins. Overall, the work discussed here reveals basic chemical and biological principles of arginine, aspartate, glutamate, and serine ADP-ribosylation and enables new strategies to interrogate the biochemical consequences of this widespread protein modification in human physiology and disease."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10072","1381370413"],"dc:language":["en"],"dc:subject":["ADP-Ribosylation","Peptides","Serine","Adenosine Diphosphate Ribose"],"dc:title":["Development and Application of Chemoenzymatic Tools to Investigate Site-Specific Protein ADP-Ribosylation"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:38Z"}