Synthetic zwitterionic streptococcus pneumoniae Type 1 oligosaccharides carrying labile O-acetyl esters

Autor: Zhen Wang, Ana Gimeno, Marta G. Lete, Herman S. Overkleeft, Gijsbert A. van der Marel, Fabrizio Chiodo, Jesús Jiménez‐Barbero, Jeroen D. C. Codée
Přispěvatelé: Molecular cell biology and Immunology, European Commission
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Angewandte Chemie (International Edition), 62(1):e202211940
Angewandte Chemie-International Edition, 62(1):e202211940. John Wiley and Sons Ltd
Wang, Z, Gimeno, A, Lete, M G, Overkleeft, H S, van der Marel, G A, Chiodo, F, Jiménez-Barbero, J & Codée, J D C 2023, ' Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O-Acetyl Esters ', Angewandte Chemie-International Edition, vol. 62, no. 1, e202211940 . https://doi.org/10.1002/anie.202211940
ISSN: 1433-7851
DOI: 10.1002/anie.202211940
Popis: We herein report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, a unique zwitterionic capsular polysaccharide carrying labile O-acetyl esters. The target oligosaccharides, featuring rare α-2,4-diamino-2,4,6-trideoxy galactose (AAT) and α-galacturonic acids, were assembled up to the 9-mer level, in a highly stereoselective manner using trisaccharide building blocks. The lability of the O-acetyl esters imposed a careful deprotection scheme to prevent migration and hydrolysis. The migration was investigated in detail at various pD values using NMR spectroscopy, to show that migration and hydrolysis of the C-3-O-acetyl esters readily takes place under neutral conditions. Structural investigation showed the oligomers to adopt a right-handed helical structure with the acetyl esters exposed on the periphery of the helix in close proximity of the neighboring AAT residues, thereby imposing conformational restrictions on the AATα1-4GalA(3OAc) glycosidic linkages, supporting the helical shape of the polysaccharide, that has been proposed to be critical for its unique biological activity. This work was supported by the Chinese Scholarship Council (CSC grant to Z. Wang), the Netherlands Organisation for Scientific Research (NWO VICI VI.C.182.020 to J.D.C.C), the European Research Council (ERC-2017-AdG, project number 788143-RE-CGLYCA NMR to J.J.B.) and Agencia Estatal de Investigación (Spain), projects RTI2018-094751-B-C21 and CIBERES, an initiative of Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Databáze: OpenAIRE
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