Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603073
Title: Design, synthesis and activity evaluation of antioxidant peptides
Author: Tegazzini, Diana
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
Availability of Full Text:
Full text unavailable from EThOS. Please contact the current institution’s library for further details.
Abstract:
Reactive Oxygen Species (ROS) produced during normal aerobic metabolism, if not promptly removed by the detoxification mechanisms of the cells, can easily react with cell components, especially lipids, producing secondary cytotoxic molecules called reactive carbonyl species (RCSs). RCSs exhibit significant chemical reactivity and can cause protein modification and dysfunction. One of the most important ReSs is 4-hydroxinonenal (HNE), an unsaturated aldehyde that has been strongly linked to Alzheimer'S disease (AD). A new series of dipeptide histidyl hydrazide analogues of carnosine was prepared, with the aim of producing molecules with enhanced HNE scavenging activity. These compounds were demonstrated to scavenge HNE and to protect SH-SY5Y cells from HNE-induced tOxlcity and were superior in action to carnosine. The synthesis of an analogue of the best compound of the series containing caffeic acid, resulted in the generation of a new molecule exhibiting complete retention of HNE-scavenging activity and also possessing free Radical Scavenging Activity (RSA). Mitochondria are the major sites of high levels of oxidative stress and the targeting of a reactive carbonyl scavenger directly to these organelles would result in extinguishing the primary source of RCS, thus arresting any consequent cellular damage. In the present work, the possibility of specifying the cellular localization of histidyl hydrazide was investigated using previously described mitochondria penetrating peptides (MPPs) and new examples of such sequences I modified to be more resistant to protease degradation. The ligation of histidyl hydrazide to a previously reported MPP was successful in targeting the former to the mitochondria of HeLa cells. Finally. a particular chemical ligation approach was investigated for the development of a system of linking a common peptide vector and a variety of cargo molecules of choice through facile in situ coupling, without requiring the de novo synthesis of a new chemical conjugate in each instance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.603073  DOI: Not available
Share: