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了解氨基酸在抗体开发中的具体影响。

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

机构信息

Innoplexus Consulting Services Pvt Ltd, 7Th Floor, Midas Tower, Hinjawadi, Pune, Maharashtra, 411057, India.

Innoplexus AG, Eschborn, Germany.

出版信息

Protein J. 2024 Jun;43(3):405-424. doi: 10.1007/s10930-024-10201-4. Epub 2024 May 9.

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.

摘要

随着人们对免疫疗法治疗和控制癌症、传染病和其他疾病的需求不断增长,对氨基酸及其在抗体工程中复杂作用的全面了解已成为首要要求。出于治疗目的,天然产生的抗体在互补决定区 (CDR) 和框架区可能没有最合适的氨基酸。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,确定对改善抗体特性有重大贡献的关键氨基酸残基至关重要。通过用高度合适的氨基酸残基进行修饰或取代,可以获得具有更高结合亲和力和改善功能的治疗性抗体。在这里,我们指出了氨基酸的频率及其与 CDR 中结合自由能的关联。该综述还分析了两项研究的实验结果,这些研究揭示了 CDR 中氨基酸的频率,并提供了它们之间的显著相关性。此外,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特性应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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