基于肽的 CE-SELEX 可方便地分离出特异性识别 CD20 表达细胞的适配体

IF 3.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2024-07-06 DOI:10.1016/j.bmc.2024.117831
Jordan Cossu , Corinne Ravelet , Véronique Martel-Frachet , Eric Peyrin , Didier Boturyn
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引用次数: 0

摘要

CD20 抗原是包括淋巴瘤和自身免疫性疾病在内的多种疾病的关键靶点。20 多年来,人们开发了多种单克隆抗体来治疗 CD20 相关疾病。然而,与许多治疗蛋白一样,这些单克隆抗体的临床应用也受到了限制,因为它们需要昂贵的生物技术程序,而且还会产生副作用,如产生抗药性中和抗体。与 mAbs 相比,核酸适配体具有一些优势,目前正在对其临床应用进行研究。我们在此报告利用基于肽的 CE-SELEX(毛细管电泳-配体的系统进化-指数富集)方法筛选 DNA 合体的情况。结果表明,这些适配体与表达 CD20 的人体细胞系特异性结合,等温滴定量热实验估计的 Kd 在微摩尔范围内。这项研究表明,CE-SELEX 适合作为传统 Cell-SELEX 的替代方法来发现新的细胞靶向化合物。
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Peptide-based CE-SELEX enables convenient isolation of aptamers specifically recognizing CD20-expressing cells

The CD20 antigen is a key target for several diseases including lymphoma and autoimmune diseases. For over 20 years, several monoclonal antibodies were developed to treat CD20-related disorders. As many therapeutic proteins, their clinical use is however limited due to their nature with a costly biotechnological procedure and side effects such as the production of anti-drug neutralizing antibodies. Nucleic acid aptamers have some advantages over mAbs and are currently investigated for clinical use. We herein report the selection of DNA aptamer by using a peptide-based CE-SELEX (Capillary Electrophoresis-Systematic Evolution of Ligands by Exponential Enrichment) method. It was demonstrated that these aptamers bind specifically a CD20-expressing human cell line, with Kd estimated from isothermal titration calorimetry experiments in the micromolar range. This study demonstrates that the CE-SELEX is suitable as alternative method to the conventional Cell-SELEX to discover new cell-targeting compounds.

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来源期刊
Bioorganic & Medicinal Chemistry
Bioorganic & Medicinal Chemistry 医学-生化与分子生物学
CiteScore
6.80
自引率
2.90%
发文量
413
审稿时长
17 days
期刊介绍: Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
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