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Probing the Limits of Q-Tag Bioconjugation of Antibodies

Lookup NU author(s): Dr James KnightORCiD

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Abstract

Site-selective labelling of antibodies (Abs) can circumvent problemsfrom heterogeneity of conventional conjugation. Here, we evaluatethe industrially-applied chemoenzymatic ‘Q-tag’ strategy based ontransglutaminase-mediated (TGase) amide-bond formation in thegeneration of 89Zr-radiolabelled antibody conjugates. We showthat, despite previously suggested high regioselectivity of TGases,in the anti-Her2 Ab Herceptint more precise native MS indicatesonly 70–80% functionalization at the target site (Q298H), in competitionwith modification at other sites, such as Q3H critically close to theCDR1 region.

Publication metadata

Author(s): Marculescu C, Lakshminarayanan A, Gault J, Knight JC, Folkes LK, Spink T, Robinson CV, Valis K, Davis BG, Cornelissen B

Publication type: Article

Publication status: Published

Journal: Chemical Communications

Year: 2019

Volume: 55

Issue: 76

Pages: 11342-11345

Print publication date: 03/09/2019

Online publication date: 03/09/2019

Acceptance date: 25/07/2019

Date deposited: 17/12/2019

ISSN (print): 1359-7345

ISSN (electronic): 1364-548X

Publisher: Roal Society of Chemistry

URL: https://doi.org/10.1039/C9CC02303H

DOI: 10.1039/C9CC02303H

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