Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
Int Immunol. 2017 Jul 1;29(7):311-317. doi: 10.1093/intimm/dxx038.
Antibodies of the IgG class carry a pair of oligosaccharides (N-glycans) in the Fc region. The importance of the N-glycan is clearly demonstrated by its profound effect in the physicochemical and biological properties of antibodies. The term 'glycoengineering' has been coined to describe contemporary strategies to improve the performance of therapeutic monoclonal antibodies on the basis of modifications in the structure and composition of the N-glycan. These methodologies have resulted in the approval and commercialization of a new generation of antibodies with improved therapeutic efficacy. So far, these advances have been driven by herculean efforts in a process of trial-and-error. The collective work of researchers in this field is progressively revealing the molecular basis of N-glycans for the function of antibodies. This knowledge will ultimately be conducive to the application of rational approaches for the successful manipulation of antibodies using glycoengineering strategies. Herein, we review advances in our understanding of the role of the N-glycan in the structural and dynamic integrity, and biological activity, of antibodies. Since the N-glycan has a multifaceted effect in antibodies, in this review we have emphasized the importance of integrating various techniques that address this problem from multiple points of view. In particular, the combination of X-ray crystallography with nuclear magnetic resonance, molecular dynamics simulations and biophysical approaches based on thermodynamic principles, has emerged as a powerful combination that is deepened our understanding of this unique system with critical implications for human well-being.
IgG 类抗体的 Fc 区域携带一对寡糖（N-聚糖）。N-聚糖的重要性通过其对抗体理化性质和生物学性质的深远影响得到了充分证明。“糖工程”这一术语被用来描述当代基于 N-聚糖结构和组成修饰来提高治疗性单克隆抗体性能的策略。这些方法已经导致了新一代具有改善治疗效果的抗体的批准和商业化。到目前为止，这些进展是通过反复试验的辛勤努力推动的。该领域研究人员的集体工作正在逐步揭示 N-聚糖对抗体功能的分子基础。这一知识最终将有助于应用合理的方法，通过糖工程策略成功地操纵抗体。本文综述了我们对 N-聚糖在抗体结构和动态完整性以及生物学活性中的作用的理解的进展。由于 N-聚糖在抗体中有多种作用，因此在本综述中，我们强调了整合从多个角度解决这一问题的各种技术的重要性。特别是，X 射线晶体学与核磁共振、分子动力学模拟和基于热力学原理的生物物理方法的结合，已经成为一种强大的组合，加深了我们对这个具有关键人类健康意义的独特系统的理解。
