Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids

被引：137

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

[21] Using genetically incorporated unnatural amino acids to control protein functions in mammalian cells
Nodling, Alexander R.
Spear, Luke A.
Williams, Thomas L.
Luk, Louis Y. P.
Tsai, Yu-Hsuan
[J]. SINGLE CELL BIOLOGY, 2019, 63 (02): : 237 - 266
[22] Site-directed spin labeling of a genetically encoded unnatural amino acid
Fleissner, Mark R.
Brustad, Eric M.
Kalai, Tamas
Altenbach, Christian
Cascio, Duilio
Peters, Francis B.
Hideg, Kalman
Peuker, Sebastian
Schultz, Peter G.
Hubbell, Wayne L.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (51) : 21637 - 21642
[23] Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids
Ilardo, Melissa
Meringer, Markus
Freeland, Stephen
Rasulev, Bakhtiyor
Cleaves, H. James, II
[J]. SCIENTIFIC REPORTS, 2015, 5
[24] Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids
Melissa Ilardo
Markus Meringer
Stephen Freeland
Bakhtiyor Rasulev
H. James Cleaves II
[J]. Scientific Reports, 5
[25] Controlling Enzyme Inhibition Using an Expanded Set of Genetically Encoded Amino Acids
Zheng, Shun
Kwon, Inchan
[J]. BIOTECHNOLOGY AND BIOENGINEERING, 2013, 110 (09) : 2361 - 2370
[26] Site-Specific Fluorescent Labeling of Purified G-Protein-Coupled Receptors Using Genetically-Encoded Unnatural Amino Acids
Ye, Shixin
Kazmi, Manija A.
Duarte, Terence
Naganathan, Saranga
Sakmar, Thomas P.
Huber, Thomas
[J]. BIOPHYSICAL JOURNAL, 2010, 98 (03) : 291A - 292A
[27] Efficient asymmetric synthesis of unnatural β-amino acids
Bolm, C
Schiffers, I
Dinter, CL
Defrère, L
Gerlach, A
Raabe, G
[J]. SYNTHESIS-STUTTGART, 2001, (11): : 1719 - 1730
[28] The large scale synthesis of unnatural amino acids
Ager, DJ
Fotheringham, IG
Laneman, SA
Pantaleone, DP
Taylor, PP
[J]. CHIMICA OGGI-CHEMISTRY TODAY, 1997, 15 (3-4) : 11 - 14
[29] The large scale synthesis of "unnatural" amino acids
Ager, DJ
Fotheringham, IG
Li, T
Pantaleone, DP
Senkpeil, RF
[J]. ENANTIOMER, 2000, 5 (3-4): : 235 - 243
[30] Recent advances in the synthesis of unnatural α-amino acids
Perdih, A.
Dolenc, M. Sollner
[J]. CURRENT ORGANIC CHEMISTRY, 2007, 11 (09) : 801 - 832

← 1 2 3 4 5 →