Weiss G A, Lowman H B
Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080, USA.
Chem Biol. 2000 Aug;7(8):R177-84. doi: 10.1016/s1074-5521(00)00016-8.
Engineering proteins to bind small molecules presents a challenge as daunting as drug discovery, for both hinge upon our understanding of receptor-ligand molecular recognition. However, powerful techniques from combinatorial molecular biology can be used to rapidly select artificial receptors. While traditionally researchers have relied upon antibody technologies as a source of new binding proteins, the lipocalin scaffold has recently emerged as an adaptable receptor for small molecule binding. 'Anticalins', engineered lipocalin variants, offer some advantages over traditional antibody technology and illuminate features of molecular recognition between receptors and small molecule ligands.
设计能结合小分子的蛋白质是一项与药物研发同样艰巨的挑战,因为二者都依赖于我们对受体-配体分子识别的理解。然而,组合分子生物学中的强大技术可用于快速筛选人工受体。传统上,研究人员依赖抗体技术作为新结合蛋白的来源,而亲脂素支架最近已成为一种适用于小分子结合的受体。“抗钙素”,即经过工程改造的亲脂素变体,相比传统抗体技术具有一些优势,并揭示了受体与小分子配体之间分子识别的特征。