Malmqvist M
Pharmacia Biosensor AB, Uppsala, Sweden.
J Mol Recognit. 1994 Mar;7(1):1-7. doi: 10.1002/jmr.300070102.
Molecular engineering of antibodies has made it possible to produce specific domains of the antibody molecule and combine them with other protein domains to achieve new properties. Using site directed mutagenesis, amino acid residues can be exchanged within the binding site; and, by analysis of crystal structures, the positions of these amino acids can be determined in three dimensions at atomic resolution. In addition, gene libraries and phage selection technology can be used to generate new antibody fragments directly from a gene pool. Both mutagenesis and selection from libraries offer opportunities to identify antibody-derived molecules with altered and useful antigen recognition properties. The detailed analysis of both kinetic and equilibrium binding affinity are therefore essential to understand the activity of the molecules resulting from antibody engineering and to guide the progress of their further design. This paper reviews recently evolving techniques for the binding analysis of antibodies, their functional domains and antibody chimerae.
抗体的分子工程使得生产抗体分子的特定结构域并将其与其他蛋白质结构域结合以获得新特性成为可能。利用定点诱变，可以在结合位点内交换氨基酸残基；并且，通过晶体结构分析，可以在原子分辨率下三维确定这些氨基酸的位置。此外，基因文库和噬菌体筛选技术可用于直接从基因库中产生新的抗体片段。诱变和从文库中筛选都为鉴定具有改变的和有用的抗原识别特性的抗体衍生分子提供了机会。因此，对动力学和平衡结合亲和力进行详细分析对于理解抗体工程产生的分子的活性以及指导其进一步设计的进展至关重要。本文综述了最近发展的用于抗体、其功能结构域和抗体嵌合体结合分析的技术。
