通过同源时间分辨 FRET 评估高亲和力单克隆抗体和抗体药物共轭物

IF 4 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2024-08-30 DOI:10.1021/acsmedchemlett.4c00317

Harmon Greenway, Jin Wang

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引用次数: 0

摘要

治疗性单克隆抗体的快速增长要求更容易获得可扩展的抗原结合评估方法。同源 TR-FRET 是初步筛选的理想方法，但由于它们的高亲和力和复杂的溶液相动力学特性，目前还没有用于检测这些相互作用的报道。在此，我们报告了一种竞争检测方法的开发情况，该方法可对这些药物与共同抗原的相对亲和力进行排序。该化验与自动化兼容，无需对分析物进行任何改动，可测量低至个位数皮摩尔的亲和力。我们进一步展示了抗体药物共轭物开发的应用。作为现有技术的低成本、高通量替代品，该测定可帮助发现和制造治疗性抗体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

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Evaluation of High-Affinity Monoclonal Antibodies and Antibody-Drug Conjugates by Homogenous Time-Resolved FRET

The rapid growth of therapeutic monoclonal antibodies demands greater accessibility to scalable methods of evaluating antigen binding. Homogenous TR-FRET is ideal for preliminary screening but has not been reported to assay these interactions due to their high-affinity and complex solution-phase kinetics. Here we report the development of a competition assay to rank-order the relative affinities of these drugs for a common antigen. The assay is compatible with automation, requires no modification of the analytes, and measures affinities as low as single-digit picomolar. We further demonstrate applications to inform the development of antibody-drug conjugates. The assay may aid discovery and manufacturing of therapeutic antibodies as a low-cost, high-throughput alternative to existing technologies.

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.