Understanding the Specific Implications of Amino Acids in the Antibody Development.

The protein journal Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI:10.1007/s10930-024-10201-4
Akshata Gavade, Anil Kumar Nagraj, Riya Patel, Roylan Pais, Pratiksha Dhanure, Juergen Scheele, Werner Seiz, Jaspal Patil
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Abstract

As the demand for immunotherapy to treat and manage cancers, infectious diseases and other disorders grows, a comprehensive understanding of amino acids and their intricate role in antibody engineering has become a prime requirement. Naturally produced antibodies may not have the most suitable amino acids at the complementarity determining regions (CDR) and framework regions, for therapeutic purposes. Therefore, to enhance the binding affinity and therapeutic properties of an antibody, the specific impact of certain amino acids on the antibody's architecture must be thoroughly studied. In antibody engineering, it is crucial to identify the key amino acid residues that significantly contribute to improving antibody properties. Therapeutic antibodies with higher binding affinity and improved functionality can be achieved through modifications or substitutions with highly suitable amino acid residues. Here, we have indicated the frequency of amino acids and their association with the binding free energy in CDRs. The review also analyzes the experimental outcome of two studies that reveal the frequency of amino acids in CDRs and provides their significant correlation between the outcomes. Additionally, it discusses the various bond interactions within the antibody structure and antigen binding. A detailed understanding of these amino acid properties should assist in the analysis of antibody sequences and structures needed for designing and enhancing the overall performance of therapeutic antibodies.

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了解氨基酸在抗体发展中的具体影响。
随着治疗和控制癌症、传染病和其他疾病的免疫疗法需求的增长,全面了解氨基酸及其在抗体工程中的复杂作用已成为首要要求。天然生产的抗体在互补决定区(CDR)和框架区可能没有最适合治疗目的的氨基酸。因此,为了提高抗体的结合亲和力和治疗特性,必须深入研究某些氨基酸对抗体结构的具体影响。在抗体工程中,找出对改善抗体特性有重大贡献的关键氨基酸残基至关重要。通过修饰或替换非常合适的氨基酸残基,可以获得具有更高的结合亲和力和更好的功能性的治疗性抗体。在此,我们指出了 CDR 中氨基酸的频率及其与结合自由能的关系。综述还分析了揭示 CDR 中氨基酸频率的两项研究的实验结果,并提供了结果之间的显著相关性。此外,它还讨论了抗体结构和抗原结合中的各种键相互作用。详细了解这些氨基酸的特性有助于分析设计和提高治疗性抗体整体性能所需的抗体序列和结构。
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