{"id":17,"date":"2019-03-13T14:08:08","date_gmt":"2019-03-13T14:08:08","guid":{"rendered":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/?page_id=17"},"modified":"2019-09-25T15:47:28","modified_gmt":"2019-09-25T15:47:28","slug":"site-selective-bioconjugation","status":"publish","type":"page","link":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/site-selective-bioconjugation\/","title":{"rendered":"Site-selective bioconjugation"},"content":{"rendered":"<p><strong><u>Highly-controlled and site-selective chemoenzymatic reactions<\/u><\/strong><\/p>\n<p>Most antibody-based PET imaging agents and antibody-drug conjugates (ADCs) are synthesised using non-selective bioconjugation methods. This involves attachment of the chelating agent or drug to amine- or carboxylic acid-containing amino acids which make up the antibody. As a result, the \u2018product\u2019 is actually a mixture of antibody-conjugates with different numbers of attachments to different sites on the antibody in a huge number of possible combinations. While most antibody-conjugates used in the clinic are made in this way, it is well-recognised that this is far from ideal because each compound in the mixture will have different pharmacological properties.<\/p>\n<p>To address this, we are researching superior <strong>chemoenzymatic <\/strong><strong>bioconjugation<\/strong><strong> strategies<\/strong> which allow the highly controlled attachment of a fixed number of chemical groups (including: radiometal chelates, near-infrared fluorophores, drugs, click chemistry reagents, and so on) to well-defined sites on the antibody structure.<\/p>\n<p>You can find out more about site-selective modifcation of antibodies <a href=\"https:\/\/pubs.rsc.org\/en\/Content\/ArticleLanding\/2019\/CC\/C9CC02303H#!divAbstract\">here<\/a>.<\/p>\n<p style=\"text-align: center\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-18\" src=\"http:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Chemoenzymatic.png\" alt=\"\" width=\"1380\" height=\"218\" srcset=\"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Chemoenzymatic.png 1380w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Chemoenzymatic-300x47.png 300w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Chemoenzymatic-768x121.png 768w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Chemoenzymatic-1024x162.png 1024w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Chemoenzymatic-500x79.png 500w\" sizes=\"auto, (max-width: 1380px) 100vw, 1380px\" \/><strong>A chemoenzymatic method for the controlled and site-selective modification of antibodies<br \/>\n<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Highly-controlled and site-selective chemoenzymatic reactions Most antibody-based PET imaging agents and antibody-drug conjugates (ADCs) are synthesised using non-selective bioconjugation methods. This involves attachment of the chelating agent or drug to amine- or carboxylic acid-containing amino acids which make up the antibody. As a result, the \u2018product\u2019 is actually a mixture of antibody-conjugates with different numbers <a href='https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/site-selective-bioconjugation\/' class='excerpt-more'>[&#8230;]<\/a><\/p>\n","protected":false},"author":3949,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-17","page","type-page","status-publish","hentry","post-seq-1","post-parity-odd","meta-position-corners","fix"],"_links":{"self":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages\/17","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/users\/3949"}],"replies":[{"embeddable":true,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/comments?post=17"}],"version-history":[{"count":8,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages\/17\/revisions"}],"predecessor-version":[{"id":173,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages\/17\/revisions\/173"}],"wp:attachment":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/media?parent=17"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}