Roberts Christopher J
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.
Trends Biotechnol. 2014 Jul;32(7):372-80. doi: 10.1016/j.tibtech.2014.05.005. Epub 2014 Jun 4.
Although it is well known that proteins are only marginally stable in their folded states, it is often less well appreciated that most proteins are inherently aggregation-prone in their unfolded or partially unfolded states, and the resulting aggregates can be extremely stable and long-lived. For therapeutic proteins, aggregates are a significant risk factor for deleterious immune responses in patients, and can form via a variety of mechanisms. Controlling aggregation using a mechanistic approach may allow improved design of therapeutic protein stability, as a complement to existing design strategies that target desired protein structures and function. Recent results highlight the importance of balancing protein environment with the inherent aggregation propensities of polypeptide chains.
虽然众所周知蛋白质在其折叠状态下仅具有一定程度的稳定性，但人们往往不太了解的是，大多数蛋白质在其未折叠或部分未折叠状态下本质上易于聚集，并且所形成的聚集体可能极其稳定且寿命很长。对于治疗性蛋白质而言，聚集体是患者产生有害免疫反应的一个重要风险因素，并且可以通过多种机制形成。使用机械方法控制聚集可能有助于改进治疗性蛋白质稳定性的设计，作为针对所需蛋白质结构和功能的现有设计策略的补充。最近的研究结果突出了平衡蛋白质环境与多肽链固有聚集倾向的重要性。
