Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Department of Digital Systems, University of Piraeus, Piraeus, Greece.
Adv Exp Med Biol. 2020;1194:359-371. doi: 10.1007/978-3-030-32622-7_34.
Monoclonal antibodies (mAbs) constitute a promising class of therapeutics, since ca. 25% of all biotech drugs in development are mAbs. Even though their therapeutic value is now well established, human- and murine-derived mAbs do have deficiencies, such as short in vivo lifespan and low stability. However, the most difficult obstacle to overcome, toward the exploitation of mAbs for disease treatment, is the prevention of the formation of protein aggregates. ANTISOMA is a pipeline for the reduction of the aggregation tendency of mAbs through the decrease in their intrinsic aggregation propensity, based on an automated amino acid substitution approach. The method takes into consideration the special features of mAbs and aims at proposing specific point mutations that could lead to the redesign of those promising therapeutics, without affecting their epitope-binding ability. The method is available online at http://bioinformatics.biol.uoa.gr/ANTISOMA .
单克隆抗体 (mAbs) 是一类很有前途的治疗药物,因为大约 25%的正在开发的生物技术药物都是 mAbs。尽管它们的治疗价值已经得到充分证实,但人和鼠源 mAbs 确实存在一些缺陷,例如体内寿命短和稳定性低。然而,在将 mAbs 用于疾病治疗方面,最困难的障碍是防止蛋白质聚集物的形成。ANTISOMA 是一种通过降低内在聚集倾向来减少 mAbs 聚集倾向的管道,它基于一种自动化的氨基酸取代方法。该方法考虑到了 mAbs 的特殊性质,旨在提出特定的点突变,从而有可能重新设计这些有前途的治疗药物,而不影响它们的抗原结合能力。该方法可在 http://bioinformatics.biol.uoa.gr/ANTISOMA 在线获得。