Saerens Dirk, Ghassabeh Gholamreza Hassanzadeh, Muyldermans Serge
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
Curr Opin Pharmacol. 2008 Oct;8(5):600-8. doi: 10.1016/j.coph.2008.07.006. Epub 2008 Aug 22.
Antibodies are large and complex molecules, with two identical parts that bind independently of each other onto the antigen and the third part of the molecule that dictates the effector function(s). To improve the therapeutic value of antibodies, protein-engineering endeavors reduced the size of the antigen-binding moiety to a single-domain unit. Occasionally, it was demonstrated that the single-domain antigen-binding derivatives of antibodies can have--on their own--an agonistic (or antagonistic) effect on their target. The small size and strict monomeric behavior, in combination with other biochemical properties such as high solubility and high specificity and affinity for the cognate antigen, make single-domain antibodies ideal to design novel man-made conjugates harnessed with innovative effector functions outside the reach of classical antibodies.
抗体是大型复杂分子,有两个彼此独立结合到抗原上的相同部分以及决定效应器功能的分子第三部分。为提高抗体的治疗价值,蛋白质工程努力将抗原结合部分的大小缩减为单结构域单元。偶尔有研究表明,抗体的单结构域抗原结合衍生物自身可对其靶标产生激动(或拮抗)作用。单结构域抗体体积小且严格呈单体行为,再加上其他生化特性,如高溶解性、高特异性以及对同源抗原的高亲和力,使其成为设计新型人工缀合物的理想选择,这些缀合物具有经典抗体所没有的创新效应器功能。