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Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies.
Ye, Farong; Zhao, Jie; Xu, Peng; Liu, Xinliang; Yu, Jing; Shangguan, Wei; Liu, Jiazhi; Luo, Xiaosheng; Li, Cheng; Ying, Tianlei; Wang, Jing; Yu, Biao; Wang, Ping.
Afiliación
  • Ye F; 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.
  • Zhao J; 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.
  • Xu P; 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.
  • Liu X; 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.
  • Yu J; 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.
  • Shangguan W; 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.
  • Liu J; 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.
  • Luo X; 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.
  • Li C; Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • Ying T; Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • Wang J; 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.
  • Yu B; Institutes for Life Sciences, School of Medicine and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangdong, 510006, China.
  • Wang P; 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.
Angew Chem Int Ed Engl ; 60(23): 12904-12910, 2021 06 01.
Article en En | MEDLINE | ID: mdl-33709491
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicoproteína de la Espiga del Coronavirus / SARS-CoV-2 / Anticuerpos Monoclonales Límite: Humans Idioma: En Revista: Angew Chem Int Ed Engl Año: 2021 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glicoproteína de la Espiga del Coronavirus / SARS-CoV-2 / Anticuerpos Monoclonales Límite: Humans Idioma: En Revista: Angew Chem Int Ed Engl Año: 2021 Tipo del documento: Article País de afiliación: China