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首页> 外文会议>World Multiconference on Systemics, Cybernetics and Informatics(SCI 2002) v.6: Industrial Systems and Engineering I; 20020714-20020718; Orlando,FL; US >Design of affinity selections of ligands from phage display libraries based on kinetic studies
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Design of affinity selections of ligands from phage display libraries based on kinetic studies

机译：基于动力学研究设计从噬菌体展示库中选择配体的亲和力

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The affinity of a ligand to its target has often been evaluated by its dissociation constant (K_D). However, K_D is a static parameter that assumes the equilibrium of a ligand reaction with a target. Since, in practical ligand applications, the reaction time is usually limited, the properties of ligands must be evaluated dynamically. A phage display system is one of the most powerful tools for isolating specific ligands such as antibodies. We established kinetic models that describe antibody-antigen reactions that incorporate the behaviors of phage antibodies into a process that isolates them from phage display libraries. Based on this model, we rationally designed experimental conditions for isolating antibodies with a high association rate constant (k_(on)), thus enabling the rapid assay of their antigens. From a customized phage antibody library in which two hypervariable regions of an original antibody are randomized, some antibodies with higher k_(on) values than the original antibody were successively isolated under the rationally designed conditions.
机译：通常通过其解离常数（K_D）评估配体对其靶标的亲和力。然而，K_D是静态参数，其假设配体反应与靶标平衡。由于在实际的配体应用中，反应时间通常受到限制，因此必须动态评估配体的性能。噬菌体展示系统是用于分离特定配体（例如抗体）的最强大工具之一。我们建立了描述抗体-抗原反应的动力学模型，该反应将噬菌体抗体的行为纳入了将其与噬菌体展示库分离的过程。基于此模型，我们合理设计了用于分离具有高缔合速率常数（k_（on））的抗体的实验条件，从而能够快速测定其抗原。从定制的噬菌体抗体库中，将原始抗体的两个高变区随机化，在合理设计的条件下，依次分离出一些k_（on）值比原始抗体高的抗体。

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