SARS-CoV-2 刺突受体结合域的合成均一糖型揭示了单克隆抗体的不同结合特征。
Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies.
机构信息
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, China.
State Key Laboratory of Bioorganic and Natural Product Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China.
出版信息
Angew Chem Int Ed Engl. 2021 Jun 1;60(23):12904-12910. doi: 10.1002/anie.202100543. Epub 2021 Apr 8.
SARS-CoV-2 attaches to its host receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of the spike protein. The RBD glycoprotein is a critical target for the development of neutralizing antibodies and vaccines against SARS-CoV-2. However, the high heterogeneity of RBD glycoforms may lead to an incomplete neutralization effect and impact the immunogenic integrity of RBD-based vaccines. Investigating the role of different carbohydrate domains is of paramount importance. Unfortunately, there is no viable method for preparing RBD glycoproteins with structurally defined glycans. Herein we describe a highly efficient and scalable strategy for the preparation of six glycosylated RBDs bearing defined structure glycoforms at T323, N331, and N343. A combination of modern oligosaccharide, peptide synthesis and recombinant protein engineering provides a robust route to decipher carbohydrate structure-function relationships.
SARS-CoV-2 通过其刺突蛋白的受体结合域（RBD）与宿主受体血管紧张素转化酶 2（ACE2）结合。RBD 糖蛋白是开发针对 SARS-CoV-2 的中和抗体和疫苗的关键靶标。然而，RBD 糖型的高度异质性可能导致不完全的中和效果，并影响基于 RBD 的疫苗的免疫原完整性。研究不同碳水化合物结构域的作用至关重要。不幸的是，目前还没有可行的方法来制备具有结构定义聚糖的 RBD 糖蛋白。在此，我们描述了一种高效且可扩展的策略，用于制备六种糖基化的 RBD，它们在 T323、N331 和 N343 处具有定义结构的糖型。现代寡糖、肽合成和重组蛋白工程的结合为解析碳水化合物结构-功能关系提供了一条可靠的途径。
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