Probing the limits of Q-tag bioconjugation of antibodies
Site-selective labelling of antibodies (Abs) can circumvent problems from heterogeneity of conventional conjugation. Here, we evaluate the industrially-applied chemoenzymatic ‘Q-tag’ strategy based on transglutaminase-mediated (TGase) amide-bond formation in the generation of 89Zr-radiolabelled anti...
| Huvudupphovsmän: | , , , , , , , , , |
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| Materialtyp: | Journal article |
| Publicerad: |
Royal Society of Chemistry
2019
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| _version_ | 1826261057009614848 |
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| author | Marculescu, C Lakshminarayanan, A Gault, J Knight, JC Folkes, LK Spink, T Robinson, CV Vallis, K Davis, BG Cornelissen, B |
| author_facet | Marculescu, C Lakshminarayanan, A Gault, J Knight, JC Folkes, LK Spink, T Robinson, CV Vallis, K Davis, BG Cornelissen, B |
| author_sort | Marculescu, C |
| collection | OXFORD |
| description | Site-selective labelling of antibodies (Abs) can circumvent problems from heterogeneity of conventional conjugation. Here, we evaluate the industrially-applied chemoenzymatic ‘Q-tag’ strategy based on transglutaminase-mediated (TGase) amide-bond formation in the generation of 89Zr-radiolabelled antibody conjugates. We show that, despite previously suggested high regioselectivity of TGases, in the anti-Her2 Ab Herceptin™ more precise native MS indicates only 70–80% functionalization at the target site (Q298H), in competition with modification at other sites, such as Q3H critically close to the CDR1 region. |
| first_indexed | 2024-03-06T19:15:34Z |
| format | Journal article |
| id | oxford-uuid:183a8b49-8ec5-4e3b-90fe-c8a2ca670dcf |
| institution | University of Oxford |
| last_indexed | 2024-03-06T19:15:34Z |
| publishDate | 2019 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:183a8b49-8ec5-4e3b-90fe-c8a2ca670dcf2022-03-26T10:42:13ZProbing the limits of Q-tag bioconjugation of antibodiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:183a8b49-8ec5-4e3b-90fe-c8a2ca670dcfSymplectic Elements at OxfordRoyal Society of Chemistry2019Marculescu, CLakshminarayanan, AGault, JKnight, JCFolkes, LKSpink, TRobinson, CVVallis, KDavis, BGCornelissen, BSite-selective labelling of antibodies (Abs) can circumvent problems from heterogeneity of conventional conjugation. Here, we evaluate the industrially-applied chemoenzymatic ‘Q-tag’ strategy based on transglutaminase-mediated (TGase) amide-bond formation in the generation of 89Zr-radiolabelled antibody conjugates. We show that, despite previously suggested high regioselectivity of TGases, in the anti-Her2 Ab Herceptin™ more precise native MS indicates only 70–80% functionalization at the target site (Q298H), in competition with modification at other sites, such as Q3H critically close to the CDR1 region. |
| spellingShingle | Marculescu, C Lakshminarayanan, A Gault, J Knight, JC Folkes, LK Spink, T Robinson, CV Vallis, K Davis, BG Cornelissen, B Probing the limits of Q-tag bioconjugation of antibodies |
| title | Probing the limits of Q-tag bioconjugation of antibodies |
| title_full | Probing the limits of Q-tag bioconjugation of antibodies |
| title_fullStr | Probing the limits of Q-tag bioconjugation of antibodies |
| title_full_unstemmed | Probing the limits of Q-tag bioconjugation of antibodies |
| title_short | Probing the limits of Q-tag bioconjugation of antibodies |
| title_sort | probing the limits of q tag bioconjugation of antibodies |
| work_keys_str_mv | AT marculescuc probingthelimitsofqtagbioconjugationofantibodies AT lakshminarayanana probingthelimitsofqtagbioconjugationofantibodies AT gaultj probingthelimitsofqtagbioconjugationofantibodies AT knightjc probingthelimitsofqtagbioconjugationofantibodies AT folkeslk probingthelimitsofqtagbioconjugationofantibodies AT spinkt probingthelimitsofqtagbioconjugationofantibodies AT robinsoncv probingthelimitsofqtagbioconjugationofantibodies AT vallisk probingthelimitsofqtagbioconjugationofantibodies AT davisbg probingthelimitsofqtagbioconjugationofantibodies AT cornelissenb probingthelimitsofqtagbioconjugationofantibodies |