Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids

被引：139

作者：

Kim, Chan Hyuk ^{[2
,3
]}

Axup, Jun Y. ^{[2
,3
]}

Dubrovska, Anna ^{[2
,3
]}

Kazane, Stephanie A. ^{[2
,3
]}

Hutchins, Benjamin A. ^{[2
,3
]}

Wold, Erik D. ^{[2
,3
]}

Smider, Vaughn V. ^{[1
]}

Schultz, Peter G. ^{[2
,3
]}

机构：

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2012年 / 134卷 / 24期

基金：

新加坡国家研究基金会;

关键词：

CANCER-THERAPY; TUMOR-CELLS; T-CELLS; FRAGMENTS; IDENTIFICATION; RESIDUES; CODE; FAB;

D O I：

10.1021/ja303904e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations.

引用

页码：9918 / 9921

页数：4

共 50 条

[41] Probing Protein-Protein Interactions with a Genetically Encoded Photo-crosslinking Amino Acid [J].

Ai, Hui-wang ;

Shen, Weijun ;

Sagi, Amit ;

Chen, Peng R. ;

Schultz, Peter G. .

CHEMBIOCHEM, 2011, 12 (12) :1854-1857

[42] Mapping a Ligand Binding Site Using Genetically Encoded Photoactivatable Crosslinkers [J].

Grunbeck, Amy ;

Huber, Thomas ;

Sakmar, Thomas P. .

G PROTEIN COUPLED RECEPTORS: STRUCTURE, 2013, 520 :307-322

[43] Making Proteins with Unnatural Amino Acids: The First Engineered Aminoacyl-tRNA Synthetase Revisited [J].

Kast, Peter .

CHEMBIOCHEM, 2011, 12 (16) :2395-2398

[44] Enantiospecific Synthesis of Genetically Encodable Fluorescent Unnatural Amino Acid L-3-(6-Acetylnaphthalen-2-ylamino)-2-aminopropanoic Acid [J].

Xiang, Zheng ;

Wang, Lei .

JOURNAL OF ORGANIC CHEMISTRY, 2011, 76 (15) :6367-6371

[45] Using a Genetically Encoded Fluorescent Amino Acid as a Site-Specific Probe to Detect Binding of Low-Molecular-Weight Compounds [J].

Ugwumba, Isaac N. ;

Ozawa, Kiyoshi ;

de la Cruz, Laura ;

Xu, Zhi-Qiang ;

Herlt, Anthony J. ;

Hadler, Kieran S. ;

Coppin, Chris ;

Brown, Susan E. ;

Schenk, Gerhard ;

Oakeshott, John G. ;

Otting, Gottfried .

ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 2011, 9 (01) :50-57

[46] Rational Evolution of Antimicrobial Peptides Containing Unnatural Amino Acids to Combat Burn Wound Infections [J].

Xiong, Meng ;

Chen, Ming ;

Zhang, Jue .

CHEMICAL BIOLOGY & DRUG DESIGN, 2016, 88 (03) :404-410

[47] Recent advancements in enzyme engineering via site-specific incorporation of unnatural amino acids [J].

Zhu, Hang-Qin ;

Tang, Xiao-Ling ;

Zheng, Ren-Chao ;

Zheng, Yu-Guo .

WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY, 2021, 37 (12)

[48] A Genetically Encoded Homocysteine Precursor to Probe Protein Active Sites and to Addict Escherichia coli to a Noncanonical Amino Acid Directly Involved in Catalysis [J].

Dunker, Clara ;

Mootz, Henning D. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2025,

[49] Enhancing activity of FcαRI-bispecific antibodies using glycoengineering [J].

Sewnath, Celine A. N. ;

Damelang, Timon ;

Bentlage, Arthur E. H. ;

ten Kroode, Luuk ;

Tuk, Cornelis W. ;

Visser, Remco ;

Wuhrer, Manfred ;

Van Coillie, Julie ;

Rispens, Theo ;

van Egmond, Marjolein ;

Vidarsson, Gestur .

JOURNAL OF IMMUNOLOGY, 2025, 214 (06) :1261-1271

[50] Genetically encoding latent bioreactive amino acids and the development of covalent protein drugs [J].

Wang, Nanxi ;

Wang, Lei .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2022, 66

← 1 2 3 4 5 →