Tailored amino acid diversity for the evolution of antibody affinity.

Tailored amino acid diversity for the evolution of antibody affinity.
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量身定制的氨基酸多样性,用于抗体亲和力的演变。

DOI:
10.4161/mabs.21728
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发表时间:
2012-11
期刊:
影响因子:
5.3
通讯作者:
Minter R
Minter R
中科院分区:
医学2区
文献类型:
--
作者:
González-Muñoz A;Bokma E;O'Shea D;Minton K;Strain M;Vousden K;Rossant C;Jermutus L;Minter R

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抗体是一类独特的蛋白质,其具有使其结合位点适应于多种抗原的高亲和力和高特异性的能力。已经对抗体序列和结构进行了许多分析,以阐明哪些氨基酸在抗体与抗原的相互作用中具有主导作用。这些研究通常没有区分在初次免疫应答中选择用于广泛抗原特异性的氨基酸和在二次免疫应答中选择用于高亲和力的氨基酸。通过研究来自体外定向进化实验的亲和力成熟抗体的大数据集,我们能够特异性地突出与亲和力改善相关的氨基酸子集。在使用定制或完全氨基酸多样化的亲和力成熟的比较中,发现定制方法在改善亲和力方面至少与传统方法一样有效,同时需要更少的诱变文库。所得序列数据还突出了进一步降低氨基酸多样性以实现高亲和力结合相互作用的潜力。
Antibodies are a unique class of proteins with the ability to adapt their binding sites for high affinity and high specificity to a multitude of antigens. Many analyses have been performed on antibody sequences and structures to elucidate which amino acids have a predominant role in antibody interactions with antigens. These studies have generally not distinguished between amino acids selected for broad antigen specificity in the primary immune response and those selected for high affinity in the secondary immune response. By studying a large data set of affinity matured antibodies derived from in vitro directed evolution experiments, we were able to specifically highlight a subset of amino acids associated with affinity improvements. In a comparison of affinity maturations using either tailored or full amino acid diversification, the tailored approach was found to be at least as effective at improving affinity while requiring fewer mutagenesis libraries than the traditional method. The resulting sequence data also highlight the potential for further reducing amino acid diversity for high affinity binding interactions.
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发表时间: 1992-08-05
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