{"id":{"repo_id":"bradford","oai_identifier":"oai:bradscholars.brad.ac.uk:10454/19699"},"canonical_url":"https://search.dev.ndltd.org/etd/bradford/oai:bradscholars.brad.ac.uk:10454/19699","repository":{"repo_id":"bradford","name":"University of Bradford","base_url":"https://bradscholars.brad.ac.uk/oai/request"},"display":{"title":"Role of N-terminal residues of CCL19 and CCL21 in binding and activation of CCR7","abstract":"Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7.","abstract_html":"Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7.","abstract_has_math":false,"creators":["Alotaibi, Mashael A.F.J."],"institution":"University of Bradford","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Afarinkia, Kamyar"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021","date_published":"2021","updated_at":"2026-07-24T01:13:57Z","subjects":["Cancer","Metastasis","Chemokines","CCR7","CCL19","CCL21","PC3","SPPS","Homology modelling","Calcium flux","Western blot"],"languages":["en"],"rights":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10454/19699","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Afarinkia, Kamyar"]},{"key":"dc:creator","label":"Author","values":["Alotaibi, Mashael A.F.J."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2023-11-22T16:06:33Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2023-11-22T16:06:33Z"]},{"key":"dc:date.issued","label":"Date","values":["2021"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Institute of Cancer Therapeutics. Faculty of Life Science"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Bradford"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cancer","Metastasis","Chemokines","CCR7","CCL19","CCL21","PC3","SPPS","Homology modelling","Calcium flux","Western blot"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10454/19699"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7."]},{"key":"dc:title","label":"Title","values":["Role of N-terminal residues of CCL19 and CCL21 in binding and activation of CCR7"]}]}],"canonical_facts":{"dc:contributor.advisor":["Afarinkia, Kamyar"],"dc:creator":["Alotaibi, Mashael A.F.J."],"dc:date.accessioned":["2023-11-22T16:06:33Z"],"dc:date.available":["2023-11-22T16:06:33Z"],"dc:date.issued":["2021"],"dc:description.abstract":["Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7."],"dc:identifier.uri":["http://hdl.handle.net/10454/19699"],"dc:language.iso":["en"],"dc:publisher.department":["Institute of Cancer Therapeutics. Faculty of Life Science"],"dc:publisher.institution":["University of Bradford"],"dc:rights":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."],"dc:subject":["Cancer","Metastasis","Chemokines","CCR7","CCL19","CCL21","PC3","SPPS","Homology modelling","Calcium flux","Western blot"],"dc:title":["Role of N-terminal residues of CCL19 and CCL21 in binding and activation of CCR7"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-24T01:13:57Z"}