Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw, Poland.
Biotechnol Adv. 2011 Jul-Aug;29(4):436-41. doi: 10.1016/j.biotechadv.2011.03.005. Epub 2011 Apr 2.
An increasing number of proteins are currently available on the market as therapeutics and this branch of the pharmaceutical industry will expand substantially during the coming years. As many diseases result from dysfunction of proteins forming multicomponent complexes, protein drugs with their inherent high specificity and affinity seem to be optimal medical agents. On the other hand, proteins are often highly instable and sensitive to degradation, which questions their applicability as effective therapeutics. Therefore, redesign and engineering of proteins is usually a required step in the present day drug development. Several approaches have been applied to optimize the protein properties central to their pharmaceutical use. This review focuses on different strategies that improve two crucial factors influencing protein drug efficiency: protein stability and its in vivo half-life. We provide examples of successful genetic and chemical modifications applied in the design of effective protein therapeutics.
目前，市场上有越来越多的蛋白质作为治疗药物，在未来几年，这个制药领域将会大幅扩张。由于许多疾病是由形成多组分复合物的蛋白质功能障碍引起的，因此具有固有高特异性和亲和力的蛋白质药物似乎是最佳的医疗药物。另一方面，蛋白质通常极不稳定且易降解，这使得它们作为有效治疗药物的适用性受到质疑。因此，蛋白质的重新设计和工程通常是当今药物开发的必要步骤。已经应用了几种方法来优化对其药物使用起核心作用的蛋白质特性。本综述重点介绍了可改善影响蛋白质药物效率的两个关键因素的不同策略：蛋白质稳定性及其体内半衰期。我们提供了成功应用于设计有效蛋白质治疗药物的遗传和化学修饰的例子。
