Design and Application of Antibody Cysteine Variants

被引：37

作者：

Voynov, Vladimir ^{[1
]}

Chennamsetty, Naresh ^{[1
]}

Kayser, Veysel ^{[1
]}

Wallny, Hans-Joachim ^{[2
]}

Helk, Bernhard ^{[2
]}

Trout, Bernhardt L. ^{[1
]}

机构：

[1] MIT, Cambridge, MA 02139 USA

[2] Novartis Pharma AG, CH-4057 Basel, Switzerland

来源：

BIOCONJUGATE CHEMISTRY | 2010年 / 21卷 / 02期

关键词：

SITE-SPECIFIC CONJUGATION; ENGINEERED HUMAN-IGG; MONOCLONAL-ANTIBODIES; ARMING ANTIBODIES; RADIOIMMUNOTHERAPY; CONFORMATIONS; RESIDUES;

D O I：

10.1021/bc900509s

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Antibodies are multidomain proteins that are extensively used as a research tool in molecular biology and as therapeutics in medicine. In many cases, antibodies are engineered to contain surface cysteines for the site-specific conjugation of payloads. These antibodies can serve as payload vehicles in targeting a diseased cell to which the conjugated molecules exercise their activity. Here, we design and analyze a set of fourteen new IgG1 cysteine variants, with at least one variant per immunoglobulin fold domain. The cross-linking propensity of these mutants correlates very well with a tool we have developed for measuring aggregation propensity in silico, called spatial aggregation propensity (SAP). Our results indicate the utility of the SAP technology in selecting antibody cysteine variants with desired properties. Moreover, the different oligomerization propensity of the variants suggests a variety of applications in molecular biology and medicine, such as payload delivery, structural analysis, electrophoresis, and chromatography.

引用

页码：385 / 392

页数：8

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