{"id":{"repo_id":"texas","oai_identifier":"oai:repositories.lib.utexas.edu:2152/19651"},"canonical_url":"https://search.dev.ndltd.org/etd/texas/oai:repositories.lib.utexas.edu:2152/19651","repository":{"repo_id":"texas","name":"University of Texas","base_url":"https://repositories.lib.utexas.edu/server/oai/request"},"display":{"title":"Structure based design of a ricin antidote","abstract":"Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10-4 M range, leaving significant room for improvement. This thesis discusses the development of a subset of inhibitors belonging to the pterin family in which amino acids have been utilized as building blocks. Inhibitors in this family have achieved a significant increase in potency, and have provided valuable structural information for further development.","abstract_html":"Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10-4 M range, leaving significant room for improvement. This thesis discusses the development of a subset of inhibitors belonging to the pterin family in which amino acids have been utilized as building blocks. Inhibitors in this family have achieved a significant increase in potency, and have provided valuable structural information for further development.","abstract_has_math":false,"creators":["Jasheway, Karl Richard"],"institution":"The University of Texas at Austin","degree_name":"Master of Arts","degree_level":"Masters","degree_discipline":"Cell and Molecular Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Robertus, Jon D."],"committee_chairs":[],"committee_members":["Hackert, Marvin L"],"year":2012,"date_issued":"2012-12","date_published":"2012-12","updated_at":"2026-07-24T05:00:54Z","subjects":["Ricin","Drug design","Pterin","Toxin","X-ray crystallography","Protein structure","Virtual drug screening"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2152/19651","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Robertus, Jon D."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Hackert, Marvin L"]},{"key":"dc:creator","label":"Author","values":["Jasheway, Karl Richard"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2013-02-27T17:29:08Z"]},{"key":"dc:date.issued","label":"Date","values":["2012-12"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Molecular Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Arts"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas at Austin"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Ricin","Drug design","Pterin","Toxin","X-ray crystallography","Protein structure","Virtual drug screening"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152/19651"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["text"]},{"key":"dc:description.abstract","label":"Abstract","values":["Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10-4 M range, leaving significant room for improvement. This thesis discusses the development of a subset of inhibitors belonging to the pterin family in which amino acids have been utilized as building blocks. Inhibitors in this family have achieved a significant increase in potency, and have provided valuable structural information for further development."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Structure based design of a ricin antidote"]}]}],"canonical_facts":{"dc:contributor.advisor":["Robertus, Jon D."],"dc:contributor.committeemember":["Hackert, Marvin L"],"dc:creator":["Jasheway, Karl Richard"],"dc:date.accessioned":["2013-02-27T17:29:08Z"],"dc:date.issued":["2012-12"],"dc:description":["text"],"dc:description.abstract":["Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10-4 M range, leaving significant room for improvement. This thesis discusses the development of a subset of inhibitors belonging to the pterin family in which amino acids have been utilized as building blocks. Inhibitors in this family have achieved a significant increase in potency, and have provided valuable structural information for further development."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/2152/19651"],"dc:language.iso":["en_US"],"dc:subject":["Ricin","Drug design","Pterin","Toxin","X-ray crystallography","Protein structure","Virtual drug screening"],"dc:title":["Structure based design of a ricin antidote"],"thesis:degree_discipline":["Cell and Molecular Biology"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Arts"],"thesis:institution_name":["The University of Texas at Austin"]},"updated_at":"2026-07-24T05:00:54Z"}