{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/12152"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/12152","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Probing the HIV reverse-transcriptase enzyme with novel bifunctional HIV-1 RT inhibitors of the general formula (NRTI)-spacer-(NNRTI)","abstract":"The high levels of resistance elicited by both nucleoside (NRTI) and non-nucleoside (NNRTI) reverse transcriptase inhibitors have prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance as well as searching for synergism between the two drug target sites on HIV reverse transcriptase (RT). The strategy involves combining two different inhibitors into a single chemical entity via a linker, with the aim of developing a mixed-site inhibitor combining the inhibitory actions of each drug. This thesis describes the rational drug-design and synthesis of nine bifunctional drugs combining a nucleos(t)ide and a non-nucleoside reverse transcriptase inhibitor linked via different non-cleavable spacers. The C-5 position of the nucleos(t)ide portion of the bifunctional was used for attachment of the spacer throughout. However, the site of attachment on the nonnucleoside drug varies according to the inhibitor type.","abstract_html":"The high levels of resistance elicited by both nucleoside (NRTI) and non-nucleoside (NNRTI) reverse transcriptase inhibitors have prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance as well as searching for synergism between the two drug target sites on HIV reverse transcriptase (RT). The strategy involves combining two different inhibitors into a single chemical entity via a linker, with the aim of developing a mixed-site inhibitor combining the inhibitory actions of each drug. This thesis describes the rational drug-design and synthesis of nine bifunctional drugs combining a nucleos(t)ide and a non-nucleoside reverse transcriptase inhibitor linked via different non-cleavable spacers. The C-5 position of the nucleos(t)ide portion of the bifunctional was used for attachment of the spacer throughout. However, the site of attachment on the nonnucleoside drug varies according to the inhibitor type.","abstract_has_math":false,"creators":["Mohamed, Ebrahim"],"institution":"Department of Chemistry","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Hunter, Roger"],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-22T22:23:27Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/12152","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hunter, Roger"]},{"key":"dc:creator","label":"Author","values":["Mohamed, Ebrahim"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-01-13T04:07:37Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-01-13T04:07:37Z"]},{"key":"dc:date.issued","label":"Date","values":["2009"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cape Town"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/12152"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Includes abstract.","Includes bibliographical references (leaves 224-233)."]},{"key":"dc:description.abstract","label":"Abstract","values":["The high levels of resistance elicited by both nucleoside (NRTI) and non-nucleoside (NNRTI) reverse transcriptase inhibitors have prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance as well as searching for synergism between the two drug target sites on HIV reverse transcriptase (RT). The strategy involves combining two different inhibitors into a single chemical entity via a linker, with the aim of developing a mixed-site inhibitor combining the inhibitory actions of each drug. This thesis describes the rational drug-design and synthesis of nine bifunctional drugs combining a nucleos(t)ide and a non-nucleoside reverse transcriptase inhibitor linked via different non-cleavable spacers. The C-5 position of the nucleos(t)ide portion of the bifunctional was used for attachment of the spacer throughout. 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The strategy involves combining two different inhibitors into a single chemical entity via a linker, with the aim of developing a mixed-site inhibitor combining the inhibitory actions of each drug. This thesis describes the rational drug-design and synthesis of nine bifunctional drugs combining a nucleos(t)ide and a non-nucleoside reverse transcriptase inhibitor linked via different non-cleavable spacers. The C-5 position of the nucleos(t)ide portion of the bifunctional was used for attachment of the spacer throughout. 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