源自治疗性抗体的单链 Fv 片段的耐热性和结合特性。

IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein Science Pub Date : 2024-07-01 DOI:10.1002/pro.5084
Takashi Tadokoro, Harumi Tsuboi, Kota Nakamura, Tetsushi Hayakawa, Reo Ohmura, Izumi Kato, Masaki Inoue, Shin-Ichi Tsunoda, Sayaka Niizuma, Yukari Okada, Satoko Otsuguro, Katsumi Maenaka
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引用次数: 0

摘要

在治疗应用中,小型抗体片段最近被用作全长单克隆抗体的替代品。单链片段抗体(scFvs)是最受欢迎的片段抗体之一,它由可变重域(VH)和可变轻域(VL)组成,并通过一个灵活的肽链连接。尽管scFvs具有这些优点,但由于其结合活性和构象稳定性难以调控,因此其应用(尤其是用于治疗目的)仍然受到限制。在这项研究中,我们构建并分析了 10 个 scFv 片段,这些片段来源于 10 种美国 FDA 批准的 mAbs 代表药物,并对它们的理化性质进行了评估。差示扫描量热分析表明,scFvs 具有相对较高但不同的热稳定性,熔化温度在 50 到 70°C 之间,并且具有不同的解折合作性。表面等离子体共振分析表明,表现出高稳定性和合作性展开的 scFvs 片段可能倾向于保持抗原结合。这项研究展示了从美国食品药物管理局批准的抗体中提取的 scFvs 的综合理化特性,为抗体的设计和开发提供了启示。
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Thermostability and binding properties of single-chained Fv fragments derived from therapeutic antibodies.

Small antibody fragments have recently been used as alternatives to full-length monoclonal antibodies in therapeutic applications. One of the most popular fragment antibodies is single-chain fragment variables (scFvs), consisting of variable heavy (VH) and variable light (VL) domains linked by a flexible peptide linker. scFvs have small molecular sizes, which enables good tissue penetration and low immunogenicity. Despite these advantages, the use of scFvs, especially for therapeutic purpose, is still limited because of the difficulty to regulate the binding activity and conformational stability. In this study, we constructed and analyzed 10 scFv fragments derived from 10 representatives of FDA-approved mAbs to evaluate their physicochemical properties. Differential scanning calorimetry analysis showed that scFvs exhibited relatively high but varied thermostability, from 50 to 70°C of melting temperatures, and different unfolding cooperativity. Surface plasmon resonance analysis revealed that scFvs fragments that exhibit high stability and cooperative unfolding likely tend to maintain antigen binding. This study demonstrated the comprehensive physicochemical properties of scFvs derived from FDA-approved antibodies, providing insights into antibody design and development.

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来源期刊
Protein Science
Protein Science 生物-生化与分子生物学
CiteScore
12.40
自引率
1.20%
发文量
246
审稿时长
1 months
期刊介绍: Protein Science, the flagship journal of The Protein Society, is a publication that focuses on advancing fundamental knowledge in the field of protein molecules. The journal welcomes original reports and review articles that contribute to our understanding of protein function, structure, folding, design, and evolution. Additionally, Protein Science encourages papers that explore the applications of protein science in various areas such as therapeutics, protein-based biomaterials, bionanotechnology, synthetic biology, and bioelectronics. The journal accepts manuscript submissions in any suitable format for review, with the requirement of converting the manuscript to journal-style format only upon acceptance for publication. Protein Science is indexed and abstracted in numerous databases, including the Agricultural & Environmental Science Database (ProQuest), Biological Science Database (ProQuest), CAS: Chemical Abstracts Service (ACS), Embase (Elsevier), Health & Medical Collection (ProQuest), Health Research Premium Collection (ProQuest), Materials Science & Engineering Database (ProQuest), MEDLINE/PubMed (NLM), Natural Science Collection (ProQuest), and SciTech Premium Collection (ProQuest).
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