Symmetry of Fv architecture is conducive to grafting a second antibody binding site in the Fv region.
Symmetry of Fv architecture is conducive to grafting a second antibody binding site in the Fv region.
复制标题
Fv结构的对称性有利于在Fv区移植第二抗体结合位点。
DOI：
10.1016/s0006-3495(96)79398-0
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Huston,JS
中科院分区：
文献类型：
--
作者：
Keck,PC;Huston,JS
已经对抗体 Fv 区进行了分子建模研究，以在约 30 kDa 的嵌合单链 Fv (chi sFv) 种类中设计第二个抗原结合位点（chi-位点）。该分析揭示了许多 Fv 区域共有的结构基础，允许将 chi 位点嫁接到与正常结合位点完全相反的 Fv 表面上。通过使用分子图形分析，嵌合互补决定区 (chi CDR) 被定义为包含来自感兴趣的抗体结合位点的大部分 CDR。 chi CDR 的链方向性与 sFv 的特定底部环的链方向性一致，这使得 chi CDR 的嫁接具有接近亲本结合位点中 CDR 的整体几何形状。对 10 种不同 Fv 晶体结构的分析表明，插入 chi CDR 的位置非常高度保守，亲本结合位点中相应的 chi CDR 边界也是如此。这项研究的结果表明，应该可以普遍地将这种方法应用于嵌合双特异性抗体结合位点（chi BABS）蛋白的开发。
Molecular modeling studies on antibody Fv regions have been pursued to design a second antigen-binding site (chi-site) in a chimeric single-chain Fv (chi sFv) species of about 30 kDa. This analysis has uncovered an architectural basis common to many Fv regions that permits grafting a chi-site onto the Fv surface that diametrically opposes the normal combining site. By using molecular graphics analysis, chimeric complementarity-determining regions (chi CDRs) were defined that comprised most of the CDRs from an antibody binding site of interest. The chain directionality of chi CDRs was consistent with that of specific bottom loops of the sFv, which allowed for grafting of chi CDRs with an overall geometry approximating CDRs in the parent combining site. Analysis of 10 different Fv crystal structures indicates that the positions for inserting chi CDRs are very highly conserved, as are the corresponding chi CDR boundaries in the parent binding site. The results of this investigation suggest that it should be possible to generally apply this approach to the development of chimeric bispecific antibody binding site (chi BABS) proteins.