Programmable Bivalent Peptide-DNA Locks for pH-Based Control of Antibody Activity.,ACS Central Science

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Programmable Bivalent Peptide-DNA Locks for pH-Based Control of Antibody Activity.
ACS Central Science ( IF 12.7 ) Pub Date : 2019-12-23 , DOI: 10.1021/acscentsci.9b00964
Wouter Engelen _{1,

2} , Kwankwan Zhu _{1,

2} , Nikita Subedi _{2,

3} , Andrea Idili ₄ , Francesco Ricci ₄ , Jurjen Tel _{2,

3} , Maarten Merkx _{1,

2}

Affiliation

The ability to control antibody activity by pH has important applications in diagnostics, therapeutic antibody targeting, and antibody-guided imaging. Here, we report the rational design of bivalent peptide-DNA ligands that allow pH-dependent control of antibody activity. Our strategy uses a pH-responsive DNA triple helix to control switching from a tight-binding bivalent peptide-DNA lock into a weaker-binding monovalent ligand. Different designs are introduced that allow antibody activation at both basic and acidic pHs, either autonomously or in the presence of an additional oligonucleotide trigger. The pH of antibody activation could be precisely tuned by changing the DNA triple helix sequence. The peptide-DNA locks allowed pH-dependent antibody targeting of tumor cells both in bulk and for single cells confined in water-in-oil microdroplets. The latter approach enables high-throughput antibody-mediated detection of single tumor cells based on their distinctive metabolic activity.

中文翻译：

可编程的二价肽-DNA锁，用于基于pH值的抗体活性控制。

通过pH控制抗体活性的能力在诊断，治疗性抗体靶向和抗体指导的成像中具有重要的应用。在这里，我们报告了二价肽-DNA配体的合理设计，该设计允许pH依赖控制抗体的活性。我们的策略使用pH响应DNA三重螺旋来控制从紧密结合的二价肽-DNA锁定转换为结合力较弱的单价配体的转换。引入了不同的设计，这些设计允许自主地或在存在其他寡核苷酸触发器的情况下在碱性和酸性pH值下激活抗体。可以通过改变DNA三重螺旋序列来精确调节抗体激活的pH。肽-DNA锁可以使pH依赖的抗体靶向肿瘤细胞，无论是散装的还是包埋在油包水微滴中的单个细胞。

更新日期：2020-01-23

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