新型蛋白质配体-亲和体研究进展

亲和体(affibody)是一种衍生于葡萄球菌A蛋白B结构域的人工蛋白质分子．B结构域含58个氨基酸，形成3个α螺旋结构，分子质量约为6.5 ku．其中第一及第二螺旋中的13个特定位点的氨基酸对其结构无明显影响，这些位点可被随机突变形成理论上可与任何靶分子结合的亲和体文库．筛选该文库可获得能与某一靶分子特异结合的亲和体．亲和体与靶分子的结合特性与抗体相似，但与抗体相比具有一些独特的优势，如：通过体外筛选即可获得，以化学合成方法或原核表达即可大量制备，分子质量小、在生物体内组织穿透性强、血浆清除率高，理化稳定性好，可以通过交联或融合表达与标记分子(如荧光蛋白、生物素等)结合而不影响其与靶分子的结合能力．亲和体可作为抗体的替代品，用于蛋白质识别、分离及纯化、实验诊断、分子显像及靶向治疗．

An Engineered Affinity Protein-affibody

Affibodies are a new class of engineered affinity proteins derived from staphyloccocal protein A (SPA) B domain. B domain is composed of 58 amino acids with a molecular mass of 6.5 ku and has a three-helical bundle structure. Thirteen amino acid positions in helix 1 and helix 2 of B domain can be randomly mutated to construct an affibody library without obvious compromise in its structural stability. Theoretically, this library contains affibodies specific to any given target. Using affinity panning, a specific affibody can be obtained. Affibody has some functional similarities with antibody. However, compared with antibody, affibody has some outstanding properties. Affibody can be obtained by in vitro selection and can be produced in large scale by chemical synthesis or prokaryotic expression. The smaller molecular size confers its higher tissue penetrativity and faster circulation clearance. Affibody has a higher physical and chemical stability than antibody. In addition, affibody can be cross-liked with or fusion co-expressed with reporter molecules such as fluorescent protein, biotin and so on. This class of engineered affinity proteins has been used in detection, separation, and purification of target proteins and, might be extensively applied in experimental diagnosis, molecular imaging and targeted therapeutics in the future.