A study of the structural correlates of affinity maturation: Antibody affinity as a function of chemical interactions, structural plasticity and stability
A study of the structural correlates of affinity maturation: Antibody affinity as a function of chemical interactions, structural plasticity and stability
复制标题
DOI：
10.1016/j.molimm.2006.05.006
复制
发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Padlan, Eduardo A.
中科院分区：
文献类型：
--
作者：
David, Maria Pamela C.;Asprer, Jonathan James T.;Padlan, Eduardo A.
由于体细胞超突变而引入抗体种系序列中的突变可导致其衍生物对其靶标具有改变的亲和力。亲和力成熟有利于选择表现出增加的亲和力的抗体。在80个高亲和力的抗甲状腺过氧化物酶序列来自6个种系的突变进行了分析的替代残基的物理化学性质，即亲水性，大小和极化，电荷和极性，在其位置和可能的溶剂可及性的上下文中。根据亲和力成熟抗体相对于种系的所得增加的化学相互作用潜力来评价这些取代的影响。分析的结果将是有用的抗体和其他蛋白质的合理设计，以改善结合性能。(c)2006爱思唯尔有限公司保留所有权利。
Mutations introduced in an antibody germline sequence as a result of somatic hypermutation could cause its derivatives to have an altered affinity for its target. Affinity maturation favors the selection of the antibodies which exhibit increased affinity. The mutations in 80 high affinity anti-thyroid peroxidase sequences derived from six germlines were analysed in terms of the physicochemical properties of the replacement residues, namely hydrophilicity, size and polarizability, and charge and polarity, in the context of its position and probable solvent accessibility. The effects of these substitutions were evaluated in terms of the resultant increased chemical interactivity potential of the affinity-matured antibodies relative to the germline. The results of the analysis would be useful in the rational design of antibodies and of other proteins for improved binding properties. (c) 2006 Elsevier Ltd. All rights reserved.