Liu Hongcheng, Gaza-Bulseco Georgeen, Faldu Dinesh, Chumsae Chris, Sun Joanne
Process Sciences Department, Abbott Bioresearch Center, 100 Research Drive, Worcester, Massachusetts 01605, USA.
J Pharm Sci. 2008 Jul;97(7):2426-47. doi: 10.1002/jps.21180.
Heterogeneity of monoclonal antibodies is common due to the various modifications introduced over the lifespan of the molecules from the point of synthesis to the point of complete clearance from the subjects. The vast number of modifications presents great challenge to the thorough characterization of the molecules. This article reviews the current knowledge of enzymatic and nonenzymatic modifications of monoclonal antibodies including the common ones such as incomplete disulfide bond formation, glycosylation, N-terminal pyroglutamine cyclization, C-terminal lysine processing, deamidation, isomerization, and oxidation, and less common ones such as modification of the N-terminal amino acids by maleuric acid and amidation of the C-terminal amino acid. In addition, noncovalent associations with other molecules, conformational diversity and aggregation of monoclonal antibodies are also discussed. Through a complete understanding of the heterogeneity of monoclonal antibodies, strategies can be employed to better identify the potential modifications and thoroughly characterize the molecules.
单克隆抗体的异质性很常见，这是由于从合成点到从受试者体内完全清除的整个生命周期中引入了各种修饰。大量的修饰给分子的全面表征带来了巨大挑战。本文综述了目前关于单克隆抗体酶促和非酶促修饰的知识，包括常见的修饰，如不完全二硫键形成、糖基化、N端焦谷氨酰胺环化、C端赖氨酸加工、脱酰胺、异构化和氧化，以及不太常见的修饰，如马来尿酸对N端氨基酸的修饰和C端氨基酸的酰胺化。此外，还讨论了与其他分子的非共价结合、单克隆抗体的构象多样性和聚集。通过全面了解单克隆抗体的异质性，可以采用策略更好地识别潜在修饰并全面表征分子。
