{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/11555"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/11555","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"The in vivo characterisation of a C-domain specific ACE inhibitor","abstract":"The ACE protein is a zinc-dependent dipeptidyl carboxypeptidase comprised of two homologous domains termed the C- and N-domain. The C-domain is primarily responsible for the catalytic production of Ang II, while the tetrapeptide acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is predominantly cleaved by the N-domain, and both domains play a role in the metabolism of vasodilatory peptide bradykinin. In the event of myocardial infarction (MI), cardiac output and blood pressure decreases, resulting in activation of the RAS and an increase in both Ang II production and bradykinin metabolism. While initially compensatory, prolonged RAS activation has been shown to have long-term detrimental effects, and pharmaceutical intervention in the form of ACE inhibition is the first line treatment following an MI event. The ACE inhibitors currently in clinical use target both domains equally, and it has been suggested that the major side-effects of this drug class are largely attributable to the inhibition of bradykinin breakdown. A novel C-domain selective ACE inhibitor lisinopril-Trp (lisW-S) incorporates a tryptophan moiety into the P2' position of the clinically available ACE inhibitor lisinopril.","abstract_html":"The ACE protein is a zinc-dependent dipeptidyl carboxypeptidase comprised of two homologous domains termed the C- and N-domain. The C-domain is primarily responsible for the catalytic production of Ang II, while the tetrapeptide acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is predominantly cleaved by the N-domain, and both domains play a role in the metabolism of vasodilatory peptide bradykinin. In the event of myocardial infarction (MI), cardiac output and blood pressure decreases, resulting in activation of the RAS and an increase in both Ang II production and bradykinin metabolism. While initially compensatory, prolonged RAS activation has been shown to have long-term detrimental effects, and pharmaceutical intervention in the form of ACE inhibition is the first line treatment following an MI event. The ACE inhibitors currently in clinical use target both domains equally, and it has been suggested that the major side-effects of this drug class are largely attributable to the inhibition of bradykinin breakdown. A novel C-domain selective ACE inhibitor lisinopril-Trp (lisW-S) incorporates a tryptophan moiety into the P2' position of the clinically available ACE inhibitor lisinopril.","abstract_has_math":false,"creators":["Sharp, Sarah-Kate"],"institution":"Department of Surgery","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Davies, Neil"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-22T22:23:35Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/11555","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Davies, Neil"]},{"key":"dc:creator","label":"Author","values":["Sharp, Sarah-Kate"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-01-06T12:05:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-01-06T12:05:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2013"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Surgery"]},{"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/11427/11555"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Includes bibliographical references."]},{"key":"dc:description.abstract","label":"Abstract","values":["The ACE protein is a zinc-dependent dipeptidyl carboxypeptidase comprised of two homologous domains termed the C- and N-domain. The C-domain is primarily responsible for the catalytic production of Ang II, while the tetrapeptide acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is predominantly cleaved by the N-domain, and both domains play a role in the metabolism of vasodilatory peptide bradykinin. In the event of myocardial infarction (MI), cardiac output and blood pressure decreases, resulting in activation of the RAS and an increase in both Ang II production and bradykinin metabolism. While initially compensatory, prolonged RAS activation has been shown to have long-term detrimental effects, and pharmaceutical intervention in the form of ACE inhibition is the first line treatment following an MI event. The ACE inhibitors currently in clinical use target both domains equally, and it has been suggested that the major side-effects of this drug class are largely attributable to the inhibition of bradykinin breakdown. A novel C-domain selective ACE inhibitor lisinopril-Trp (lisW-S) incorporates a tryptophan moiety into the P2' position of the clinically available ACE inhibitor lisinopril."]},{"key":"dc:title","label":"Title","values":["The in vivo characterisation of a C-domain specific ACE inhibitor"]}]}],"canonical_facts":{"dc:contributor.advisor":["Davies, Neil"],"dc:creator":["Sharp, Sarah-Kate"],"dc:date.accessioned":["2015-01-06T12:05:05Z"],"dc:date.available":["2015-01-06T12:05:05Z"],"dc:date.issued":["2013"],"dc:description":["Includes bibliographical references."],"dc:description.abstract":["The ACE protein is a zinc-dependent dipeptidyl carboxypeptidase comprised of two homologous domains termed the C- and N-domain. The C-domain is primarily responsible for the catalytic production of Ang II, while the tetrapeptide acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is predominantly cleaved by the N-domain, and both domains play a role in the metabolism of vasodilatory peptide bradykinin. In the event of myocardial infarction (MI), cardiac output and blood pressure decreases, resulting in activation of the RAS and an increase in both Ang II production and bradykinin metabolism. While initially compensatory, prolonged RAS activation has been shown to have long-term detrimental effects, and pharmaceutical intervention in the form of ACE inhibition is the first line treatment following an MI event. The ACE inhibitors currently in clinical use target both domains equally, and it has been suggested that the major side-effects of this drug class are largely attributable to the inhibition of bradykinin breakdown. A novel C-domain selective ACE inhibitor lisinopril-Trp (lisW-S) incorporates a tryptophan moiety into the P2' position of the clinically available ACE inhibitor lisinopril."],"dc:identifier.uri":["http://hdl.handle.net/11427/11555"],"dc:language.iso":["eng"],"dc:publisher.department":["Department of Surgery"],"dc:publisher.institution":["University of Cape Town"],"dc:title":["The in vivo characterisation of a C-domain specific ACE inhibitor"],"dc:type":["Doctoral Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-22T22:23:35Z"}