Reducing the aggregation of proteins is of utmost interest to the pharmaceutical industry. Aggregated proteins are often less active and can cause severe immune reactions in the patient upon administration. At the same time the biopharmaceutical market is pushing for high concentration formulations and products that do not require refrigerated storage conditions. For a given protein, the only solution pH, ionic strength and concentration of a very limited number of excipients are the only parameters that can be varied to obtain a stable formulation. In this work, we present a structure-based approach to discover new molecules that successfully reduce the aggregation of proteins and apply the approach to the model protein Interferon-alpha-2a.

减少蛋白质的聚集是制药工业最感兴趣的。聚集的蛋白质通常活性较低，在给药后会引起严重的免疫反应。同时，生物制药市场正在推动不需要冷藏条件的高浓度制剂和产品。对于给定的蛋白质，唯一的溶液pH，离子强度和非常有限数量的赋形剂浓度是可以改变以获得稳定制剂的唯一参数。在这项工作中，我们提出了一种基于结构的方法来发现能够成功减少蛋白质聚集的新分子，并将该方法应用于模型蛋白质干扰素-α-2a。