Barredo-Vacchelli Gabriela R, Giudicessi Silvana L, Martínez-Ceron María C, Cascone Osvaldo, Camperi Silvia A
Facultad de Farmacia y Bioquímica, Cátedra de Biotecnología, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
Instituto de Nanobiotecnología (NANOBIOTEC), Universidad de Buenos Aires (UBA) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Junín 956, 1113 Buenos Aires, Argentina.
Int J Pept Res Ther. 2021;27(4):2905-2921. doi: 10.1007/s10989-021-10299-5. Epub 2021 Oct 19.
The interest in therapeutic monoclonal antibodies (mAbs) has significantly grown in the pharmaceutical industry, exceeding 100 FDA mAbs approved. Although the upstream processing of their industrial production has been significantly improved in the last years, the downstream processing still depends on immobilized protein A affinity chromatography. The high cost, low capacity and short half-life of immobilized protein A chromatography matrices, encouraged the design of alternative short-peptide ligands for mAb purification. Most of these peptides have been obtained by screening combinatorial peptide libraries. These low-cost ligands can be easily produced by solid-phase peptide synthesis and can be immobilized on chromatographic supports, thus obtaining matrices with high capacity and selectivity. Furthermore, matrices with immobilized peptide ligands have longer half-life than those with protein A due to the higher stability of the peptides. In this review the design and synthesis of peptide ligands, their immobilization on chromatographic supports and the evaluation of the affinity supports for their application in mAb purification is described.
制药行业对治疗性单克隆抗体（mAb）的兴趣显著增长，已有超过100种单克隆抗体获得美国食品药品监督管理局（FDA）批准。尽管近年来其工业生产的上游工艺有了显著改进，但下游工艺仍依赖于固定化蛋白A亲和色谱法。固定化蛋白A色谱基质成本高、容量低且半衰期短，这促使人们设计用于单克隆抗体纯化的替代短肽配体。这些肽大多是通过筛选组合肽库获得的。这些低成本配体可通过固相肽合成轻松制备，并可固定在色谱支持物上，从而获得具有高容量和选择性的基质。此外，由于肽的稳定性更高，固定化肽配体的基质比蛋白A基质具有更长的半衰期。本文综述了肽配体的设计与合成、其在色谱支持物上的固定化以及用于单克隆抗体纯化的亲和支持物的评估。
