Probing the limits of Q-tag bioconjugation of antibodies

被引：15

作者：

Marculescu, Cristina ^{[1
,2
]}

Lakshminarayanan, Abirami ^{[1
,2
]}

Gault, Joseph ^{[2
]}

Knight, James C. ^{[1
]}

Folkes, Lisa K. ^{[1
]}

Spink, Thomas ^{[1
]}

Robinson, Carol, V ^{[2
]}

Vallis, Katherine ^{[1
]}

Davis, Benjamin G. ^{[2
]}

Cornelissen, Bart ^{[1
]}

机构：

[1] Univ Oxford, Dept Oncol, CRUK MRC Oxford Inst Radiat Oncol, Oxford OX3 7DQ, England

[2] Univ Oxford, Chem Res Lab, Oxford OX1 3TA, England

来源：

CHEMICAL COMMUNICATIONS | 2019年 / 55卷 / 76期

基金：

英国工程与自然科学研究理事会; 英国惠康基金;

关键词：

SITE-SPECIFIC CONJUGATION; PET; GLYCOSYLATION; ZR-89-TRASTUZUMAB; PHARMACOKINETICS; TRANSGLUTAMINASE; TRASTUZUMAB; STABILITY; BACTERIAL; STRATEGY;

D O I：

10.1039/c9cc02303h

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 Zr-89-radiolabelled antibody conjugates. We show that, despite previously suggested high regioselectivity of TGases, in the anti-Her2 Ab Herceptin (TM) more precise native MS indicates only 70-80% functionalization at the target site (Q298(H)), in competition with modification at other sites, such as Q3(H) critically close to the CDR1 region.

引用

页码：11342 / 11345

页数：4

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