{"id":{"repo_id":"texas","oai_identifier":"oai:repositories.lib.utexas.edu:2152/135853"},"canonical_url":"https://search.dev.ndltd.org/etd/texas/oai:repositories.lib.utexas.edu:2152/135853","repository":{"repo_id":"texas","name":"University of Texas","base_url":"https://repositories.lib.utexas.edu/server/oai/request"},"display":{"title":"Synthesis of cis- and trans-3-fluoroacrylate, and inhibition of BCL6 targeting a non-reactive cysteine","abstract":"Synthetic routes have been developed for two substrates for one project and an inhibitor in a second project. In the first project, synthetic routes were devised to make the cis- and trans-isomers of 3-flouroacrylate. In both cases, the compounds were successfully made in a four-step procedure. In future work, the compounds will be tested with cis- and trans-3-haloacrylate dehalogenase that has been shown to process the corresponding chloro- and bromo- isomers in an isomer-specific manner. These compounds might be processed like the other halo-acrylates (where the halo group if chloro or bromo) or might function as inhibitors if the enzyme proceeds through a halohydrin intermediate. In the second project, a potential inhibitor that targets the BTB-domain of BCL6 was made in a multi-step route. The compound builds on preliminary data that shows a “switchable electrophile” strategy can be used to selectively and irreversibly modify a cysteine within the corepressor peptide binding site in the BTB-domain of BCL6. Irreversible inhibition will block its function. These inhibitors are potential therapeutics for treating diffuse large B-cell lymphomas (DLBCLs) and triple negative breast cancers that are BCL6-dependent. In future work, the compound will be tested to validate the design principle. The results will guide the development of more potent and specific therapeutic agents.","abstract_html":"Synthetic routes have been developed for two substrates for one project and an inhibitor in a second project. In the first project, synthetic routes were devised to make the cis- and trans-isomers of 3-flouroacrylate. In both cases, the compounds were successfully made in a four-step procedure. In future work, the compounds will be tested with cis- and trans-3-haloacrylate dehalogenase that has been shown to process the corresponding chloro- and bromo- isomers in an isomer-specific manner. These compounds might be processed like the other halo-acrylates (where the halo group if chloro or bromo) or might function as inhibitors if the enzyme proceeds through a halohydrin intermediate. In the second project, a potential inhibitor that targets the BTB-domain of BCL6 was made in a multi-step route. The compound builds on preliminary data that shows a “switchable electrophile” strategy can be used to selectively and irreversibly modify a cysteine within the corepressor peptide binding site in the BTB-domain of BCL6. Irreversible inhibition will block its function. These inhibitors are potential therapeutics for treating diffuse large B-cell lymphomas (DLBCLs) and triple negative breast cancers that are BCL6-dependent. In future work, the compound will be tested to validate the design principle. The results will guide the development of more potent and specific therapeutic agents.","abstract_has_math":false,"creators":["Quintana Caban, Leugim J."],"institution":"The University of Texas at Austin","degree_name":"Master of Science in Pharmaceutical Sciences","degree_level":"Masters","degree_discipline":"Medicinal Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Whitman, Christian P."],"committee_chairs":[],"committee_members":["Hoffman, David W"],"year":2025,"date_issued":"2025-12","date_published":"2025-12","updated_at":"2026-07-24T05:01:04Z","subjects":["Dehalogenase","Acrylate","Suicide inhibitor","BCL6"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://doi.org/10.26153/tsw/63167"],"render_values":[{"text":"https://doi.org/10.26153/tsw/63167","href":"https://doi.org/10.26153/tsw/63167","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152/135853","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Whitman, Christian P."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Hoffman, David W"]},{"key":"dc:creator","label":"Author","values":["Quintana Caban, Leugim J."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-04-07T01:57:08Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-12"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Medicinal Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science in Pharmaceutical Sciences"]},{"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":["Dehalogenase","Acrylate","Suicide inhibitor","BCL6"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152/135853","https://doi.org/10.26153/tsw/63167"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Synthetic routes have been developed for two substrates for one project and an inhibitor in a second project. In the first project, synthetic routes were devised to make the cis- and trans-isomers of 3-flouroacrylate. In both cases, the compounds were successfully made in a four-step procedure. In future work, the compounds will be tested with cis- and trans-3-haloacrylate dehalogenase that has been shown to process the corresponding chloro- and bromo- isomers in an isomer-specific manner. These compounds might be processed like the other halo-acrylates (where the halo group if chloro or bromo) or might function as inhibitors if the enzyme proceeds through a halohydrin intermediate. In the second project, a potential inhibitor that targets the BTB-domain of BCL6 was made in a multi-step route. The compound builds on preliminary data that shows a “switchable electrophile” strategy can be used to selectively and irreversibly modify a cysteine within the corepressor peptide binding site in the BTB-domain of BCL6. Irreversible inhibition will block its function. These inhibitors are potential therapeutics for treating diffuse large B-cell lymphomas (DLBCLs) and triple negative breast cancers that are BCL6-dependent. In future work, the compound will be tested to validate the design principle. The results will guide the development of more potent and specific therapeutic agents."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Synthesis of cis- and trans-3-fluoroacrylate, and inhibition of BCL6 targeting a non-reactive cysteine"]}]}],"canonical_facts":{"dc:contributor.advisor":["Whitman, Christian P."],"dc:contributor.committeemember":["Hoffman, David W"],"dc:creator":["Quintana Caban, Leugim J."],"dc:date.accessioned":["2026-04-07T01:57:08Z"],"dc:date.issued":["2025-12"],"dc:description.abstract":["Synthetic routes have been developed for two substrates for one project and an inhibitor in a second project. In the first project, synthetic routes were devised to make the cis- and trans-isomers of 3-flouroacrylate. In both cases, the compounds were successfully made in a four-step procedure. In future work, the compounds will be tested with cis- and trans-3-haloacrylate dehalogenase that has been shown to process the corresponding chloro- and bromo- isomers in an isomer-specific manner. These compounds might be processed like the other halo-acrylates (where the halo group if chloro or bromo) or might function as inhibitors if the enzyme proceeds through a halohydrin intermediate. In the second project, a potential inhibitor that targets the BTB-domain of BCL6 was made in a multi-step route. The compound builds on preliminary data that shows a “switchable electrophile” strategy can be used to selectively and irreversibly modify a cysteine within the corepressor peptide binding site in the BTB-domain of BCL6. Irreversible inhibition will block its function. These inhibitors are potential therapeutics for treating diffuse large B-cell lymphomas (DLBCLs) and triple negative breast cancers that are BCL6-dependent. In future work, the compound will be tested to validate the design principle. The results will guide the development of more potent and specific therapeutic agents."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2152/135853","https://doi.org/10.26153/tsw/63167"],"dc:subject":["Dehalogenase","Acrylate","Suicide inhibitor","BCL6"],"dc:title":["Synthesis of cis- and trans-3-fluoroacrylate, and inhibition of BCL6 targeting a non-reactive cysteine"],"dc:type":["Thesis"],"thesis:degree_discipline":["Medicinal Chemistry"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Science in Pharmaceutical Sciences"],"thesis:institution_name":["The University of Texas at Austin"]},"updated_at":"2026-07-24T05:01:04Z"}