Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O-Acetyl Esters

Area of Science:

• Carbohydrate Chemistry
• Structural Biology
• Microbiology

Background:

• Streptococcus pneumoniae serotype 1 (Sp1) produces a unique zwitterionic capsular polysaccharide.
• This polysaccharide contains rare amino sugars and labile O-acetyl esters, crucial for its biological activity.
• Understanding Sp1 structure is key to developing targeted therapies.

Purpose of the Study:

• To achieve the first total synthesis of the Sp1 oligosaccharide.
• To investigate the stability and migration of O-acetyl esters.
• To elucidate the structure and conformational properties of the synthesized Sp1 oligomers.

Main Methods:

• Stereoselective synthesis using trisaccharide building blocks.
• Detailed NMR spectroscopy for migration studies at various pD values.
• Structural analysis to determine oligomer conformation.

Main Results:

• Successful synthesis of Sp1 oligosaccharides up to the 9-mer level.
• Demonstrated lability and migration of C-3-O-acetyl esters under neutral conditions.
• Revealed a right-handed helical structure with peripheral O-acetyl esters influencing AAT-GalA glycosidic linkages.

Conclusions:

• The total synthesis of Sp1 oligosaccharide was accomplished.
• O-acetyl ester lability necessitates careful handling during synthesis and analysis.
• The determined helical structure provides insights into the polysaccharide's biological function.