{"id":{"repo_id":"strathclyde","oai_identifier":"oai:strathclyde:k3569439q"},"canonical_url":"https://search.dev.ndltd.org/etd/strathclyde/oai:strathclyde:k3569439q","repository":{"repo_id":"strathclyde","name":"University of Strathclyde","base_url":"https://stax.strath.ac.uk/catalog/oai"},"display":{"title":"Building a rational model for the identification of allosteric sites","abstract":"Allostery is the regulation of protein function, structure and/or flexibility that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no definitive technique has yet been identified to distinguish these allosteric sites. Al-Shar'i developed a new technique using a combination of fluctuation analysis, cross correlation, simple intrasequence difference (SID) and energy analysis.3 A potential site has been determined for the protein kinase DYRK2 using this technique. The potential allosteric pocket was studied through a virtual screen which gave a hit that was successfully prepared and showed good selectivity for DYRK2 over DYRK1A by Differential Scanning Fluorimetry (DSF). This oxyamidine hit was further investigated through a structure activity relationship (SAR) which enabled the synthesis of three compounds that showed a higher stabilization than the initial hit (Tm > 1.2 °C). A second library was synthesized based on the same core, but with an amide functionality instead of an oxyamidine. From this new library, a SAR study was also carried out. This led to the synthesis of five analogues that have shown great binding activity (IC50 < 240nM) and selectivity for DYRK2.","abstract_html":"Allostery is the regulation of protein function, structure and/or flexibility that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no definitive technique has yet been identified to distinguish these allosteric sites. Al-Shar&#x27;i developed a new technique using a combination of fluctuation analysis, cross correlation, simple intrasequence difference (SID) and energy analysis.3 A potential site has been determined for the protein kinase DYRK2 using this technique. The potential allosteric pocket was studied through a virtual screen which gave a hit that was successfully prepared and showed good selectivity for DYRK2 over DYRK1A by Differential Scanning Fluorimetry (DSF). This oxyamidine hit was further investigated through a structure activity relationship (SAR) which enabled the synthesis of three compounds that showed a higher stabilization than the initial hit (Tm &gt; 1.2 °C). A second library was synthesized based on the same core, but with an amide functionality instead of an oxyamidine. From this new library, a SAR study was also carried out. This led to the synthesis of five analogues that have shown great binding activity (IC50 &lt; 240nM) and selectivity for DYRK2.","abstract_has_math":false,"creators":["Indey, Camille Roxanne Chevalier"],"institution":"University of Strathclyde","degree_name":"phd","degree_level":"doctoral-pg","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-24T04:50:43Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.48730/8qyh-ny81"],"render_values":[{"text":"10.48730/8qyh-ny81","href":"https://doi.org/10.48730/8qyh-ny81","code":true}]},{"key":"dc:identifier","label":"Identifier","values":["T14284"],"render_values":[{"text":"T14284","href":null,"code":true}]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["201266694"],"render_values":[{"text":"201266694","href":null,"code":true}]}]},"links":{"outbound_url":"https://stax.strath.ac.uk/concern/theses/k3569439q","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Indey, Camille Roxanne Chevalier"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["201266694"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016"]},{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Pure and Applied Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Strathclyde"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral-pg"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["T14284"]},{"key":"dc:identifier.doi","label":"DOI","values":["10.48730/8qyh-ny81"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://stax.strath.ac.uk/concern/theses/k3569439q"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Allostery is the regulation of protein function, structure and/or flexibility that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no definitive technique has yet been identified to distinguish these allosteric sites. Al-Shar'i developed a new technique using a combination of fluctuation analysis, cross correlation, simple intrasequence difference (SID) and energy analysis.3 A potential site has been determined for the protein kinase DYRK2 using this technique. The potential allosteric pocket was studied through a virtual screen which gave a hit that was successfully prepared and showed good selectivity for DYRK2 over DYRK1A by Differential Scanning Fluorimetry (DSF). This oxyamidine hit was further investigated through a structure activity relationship (SAR) which enabled the synthesis of three compounds that showed a higher stabilization than the initial hit (Tm > 1.2 °C). A second library was synthesized based on the same core, but with an amide functionality instead of an oxyamidine. From this new library, a SAR study was also carried out. This led to the synthesis of five analogues that have shown great binding activity (IC50 < 240nM) and selectivity for DYRK2."]},{"key":"dc:description.abstract","label":"Abstract","values":["Allostery is the regulation of protein function, structure and/or flexibility that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no definitive technique has yet been identified to distinguish these allosteric sites. Al-Shar'i developed a new technique using a combination of fluctuation analysis, cross correlation, simple intrasequence difference (SID) and energy analysis.3 A potential site has been determined for the protein kinase DYRK2 using this technique. The potential allosteric pocket was studied through a virtual screen which gave a hit that was successfully prepared and showed good selectivity for DYRK2 over DYRK1A by Differential Scanning Fluorimetry (DSF). This oxyamidine hit was further investigated through a structure activity relationship (SAR) which enabled the synthesis of three compounds that showed a higher stabilization than the initial hit (Tm > 1.2 °C). A second library was synthesized based on the same core, but with an amide functionality instead of an oxyamidine. From this new library, a SAR study was also carried out. This led to the synthesis of five analogues that have shown great binding activity (IC50 < 240nM) and selectivity for DYRK2."]},{"key":"dc:title","label":"Title","values":["Building a rational model for the identification of allosteric sites"]}]}],"canonical_facts":{"dc:creator":["Indey, Camille Roxanne Chevalier"],"dc:creator.authoridentifier":["201266694"],"dc:date":["2016"],"dc:date.issued":["2016"],"dc:description":["Allostery is the regulation of protein function, structure and/or flexibility that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no definitive technique has yet been identified to distinguish these allosteric sites. Al-Shar'i developed a new technique using a combination of fluctuation analysis, cross correlation, simple intrasequence difference (SID) and energy analysis.3 A potential site has been determined for the protein kinase DYRK2 using this technique. The potential allosteric pocket was studied through a virtual screen which gave a hit that was successfully prepared and showed good selectivity for DYRK2 over DYRK1A by Differential Scanning Fluorimetry (DSF). This oxyamidine hit was further investigated through a structure activity relationship (SAR) which enabled the synthesis of three compounds that showed a higher stabilization than the initial hit (Tm > 1.2 °C). A second library was synthesized based on the same core, but with an amide functionality instead of an oxyamidine. From this new library, a SAR study was also carried out. This led to the synthesis of five analogues that have shown great binding activity (IC50 < 240nM) and selectivity for DYRK2."],"dc:description.abstract":["Allostery is the regulation of protein function, structure and/or flexibility that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no definitive technique has yet been identified to distinguish these allosteric sites. Al-Shar'i developed a new technique using a combination of fluctuation analysis, cross correlation, simple intrasequence difference (SID) and energy analysis.3 A potential site has been determined for the protein kinase DYRK2 using this technique. The potential allosteric pocket was studied through a virtual screen which gave a hit that was successfully prepared and showed good selectivity for DYRK2 over DYRK1A by Differential Scanning Fluorimetry (DSF). This oxyamidine hit was further investigated through a structure activity relationship (SAR) which enabled the synthesis of three compounds that showed a higher stabilization than the initial hit (Tm > 1.2 °C). A second library was synthesized based on the same core, but with an amide functionality instead of an oxyamidine. From this new library, a SAR study was also carried out. This led to the synthesis of five analogues that have shown great binding activity (IC50 < 240nM) and selectivity for DYRK2."],"dc:identifier":["T14284"],"dc:identifier.doi":["10.48730/8qyh-ny81"],"dc:identifier.uri":["https://stax.strath.ac.uk/concern/theses/k3569439q"],"dc:publisher.department":["Department of Pure and Applied Chemistry"],"dc:publisher.institution":["University of Strathclyde"],"dc:title":["Building a rational model for the identification of allosteric sites"],"dc:type.qualificationlevel":["doctoral-pg"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T04:50:43Z"}