Drug Discovery, Biogen IDEC Inc., 12 Cambridge Center, Cambridge, MA 02142, United States.
Curr Opin Chem Biol. 2010 Aug;14(4):520-8. doi: 10.1016/j.cbpa.2010.06.175. Epub 2010 Jul 16.
Since the first protein therapeutics were approved two decades ago, the field has seen a transition from the development of naturally occurring proteins to design of molecules engineered for optimal target recognition, pharmacokinetics, biodistribution, and therapeutic function. Many modified antibodies and monovalent or multispecific antibody-like molecules with custom profiles are in different stages of drug development. In addition, several non-antibody protein scaffolds that interrogate a broad range of targets are being pursued. As protein engineering efforts have expanded and diversified, it has become increasingly important to understand the biophysical and biochemical properties of proteins and to translate this knowledge into design of optimized pharmaceutical agents.
自二十年前批准了第一批蛋白质治疗药物以来,该领域已经从开发天然存在的蛋白质转变为设计针对最佳靶标识别、药代动力学、生物分布和治疗功能的分子。许多具有定制特征的经过修饰的抗体和单价或多特异性抗体样分子处于不同的药物开发阶段。此外,正在探索几种可检测广泛靶标的非抗体蛋白支架。随着蛋白质工程的不断扩展和多样化,了解蛋白质的物理化学性质并将这些知识转化为优化药物设计变得越来越重要。