{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/27538"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/27538","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Design and Synthesis of Hyaluronan:RHAMM Interaction Inhibitors","abstract":"A major component of the extracellular matrix is hyaluronan, a regulator of cell migration/survival and differentiation during response-to-injury processes. The receptor for hyaluronan-mediated motility (RHAMM) binds to HA and has limited constitutive expression but is upregulated during tissue injury. Blocking HA fragment:RHAMM interactions has therapeutic potential for treating cancer but truncation of RHAMM into peptides mimicking only the HA binding domains is predicted to lose their natural α-helical structure. The goal of this project is to explore the effects cyclizing each binding domain has on helicity and its biological effect. Eighteen peptides were synthesized and cyclized using lactam bridges. The peptides were analyzed by circular dichroism spectroscopy and one stapled peptide exhibited a 4-fold increase in helicity compared to the unstapled sequence and significantly decreased migration, inflammation, and fibrosis in vitro. This cyclic peptide is a novel protein-carbohydrate inhibitor and has the potential to be a therapeutic in the cancer treatment.","abstract_html":"A major component of the extracellular matrix is hyaluronan, a regulator of cell migration/survival and differentiation during response-to-injury processes. The receptor for hyaluronan-mediated motility (RHAMM) binds to HA and has limited constitutive expression but is upregulated during tissue injury. Blocking HA fragment:RHAMM interactions has therapeutic potential for treating cancer but truncation of RHAMM into peptides mimicking only the HA binding domains is predicted to lose their natural α-helical structure. The goal of this project is to explore the effects cyclizing each binding domain has on helicity and its biological effect. Eighteen peptides were synthesized and cyclized using lactam bridges. The peptides were analyzed by circular dichroism spectroscopy and one stapled peptide exhibited a 4-fold increase in helicity compared to the unstapled sequence and significantly decreased migration, inflammation, and fibrosis in vitro. This cyclic peptide is a novel protein-carbohydrate inhibitor and has the potential to be a therapeutic in the cancer treatment.","abstract_has_math":false,"creators":["Rodrigues, Emily"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Len Luyt"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-08-10","date_published":"2017-08-10","updated_at":"2026-07-27T21:56:20Z","subjects":["Peptide","cyclization","alpha helix","receptor for hyaluronan mediated motility","hyaluronan","cancer"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/27538","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Len Luyt"]},{"key":"dc:creator","label":"Author","values":["Rodrigues, Emily"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T15:30:33Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T15:30:33Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-08-10"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Peptide","cyclization","alpha helix","receptor for hyaluronan mediated motility","hyaluronan","cancer"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/27538"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["A major component of the extracellular matrix is hyaluronan, a regulator of cell migration/survival and differentiation during response-to-injury processes. The receptor for hyaluronan-mediated motility (RHAMM) binds to HA and has limited constitutive expression but is upregulated during tissue injury. Blocking HA fragment:RHAMM interactions has therapeutic potential for treating cancer but truncation of RHAMM into peptides mimicking only the HA binding domains is predicted to lose their natural α-helical structure. The goal of this project is to explore the effects cyclizing each binding domain has on helicity and its biological effect. Eighteen peptides were synthesized and cyclized using lactam bridges. The peptides were analyzed by circular dichroism spectroscopy and one stapled peptide exhibited a 4-fold increase in helicity compared to the unstapled sequence and significantly decreased migration, inflammation, and fibrosis in vitro. This cyclic peptide is a novel protein-carbohydrate inhibitor and has the potential to be a therapeutic in the cancer treatment."]},{"key":"dc:title","label":"Title","values":["Design and Synthesis of Hyaluronan:RHAMM Interaction Inhibitors"]}]}],"canonical_facts":{"dc:contributor.advisor":["Len Luyt"],"dc:creator":["Rodrigues, Emily"],"dc:date.accessioned":["2025-07-10T15:30:33Z"],"dc:date.available":["2025-07-10T15:30:33Z"],"dc:date.issued":["2017-08-10"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["A major component of the extracellular matrix is hyaluronan, a regulator of cell migration/survival and differentiation during response-to-injury processes. The receptor for hyaluronan-mediated motility (RHAMM) binds to HA and has limited constitutive expression but is upregulated during tissue injury. Blocking HA fragment:RHAMM interactions has therapeutic potential for treating cancer but truncation of RHAMM into peptides mimicking only the HA binding domains is predicted to lose their natural α-helical structure. The goal of this project is to explore the effects cyclizing each binding domain has on helicity and its biological effect. Eighteen peptides were synthesized and cyclized using lactam bridges. The peptides were analyzed by circular dichroism spectroscopy and one stapled peptide exhibited a 4-fold increase in helicity compared to the unstapled sequence and significantly decreased migration, inflammation, and fibrosis in vitro. This cyclic peptide is a novel protein-carbohydrate inhibitor and has the potential to be a therapeutic in the cancer treatment."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/27538"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Peptide","cyclization","alpha helix","receptor for hyaluronan mediated motility","hyaluronan","cancer"],"dc:title":["Design and Synthesis of Hyaluronan:RHAMM Interaction Inhibitors"],"dc:type":["thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:20Z"}