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Design, Synthesis, and Characterization of Stapled Oligosaccharides.

ABSTRACT: Stapling short peptides to lock specific conformations and thereby obtain superior pharmacological properties is well established. However, similar concepts have not been applied to oligosaccharides. Here, we describe the design, synthesis, and characterization of the first stapled oligosaccharides. Automated assembly of β-(1,6)-glucans equipped with two alkenyl side chains was followed by on-resin Grubbs metathesis for efficient ring closure with a variety of cross-linkers of different sizes. Oligosaccharide stapling increases enzymatic stability and cell penetration, therefore opening new opportunities for the use of glycans in medicinal chemistry.

SUBMITTER: Ricardo MG

PROVIDER: S-EPMC9562281 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Characterization of Stapled Oligosaccharides.

Ricardo Manuel G MG Reuber Emelie E EE Yao Ling L Danglad-Flores José J Delbianco Martina M Seeberger Peter H PH

Journal of the American Chemical Society 20220929 40

Stapling short peptides to lock specific conformations and thereby obtain superior pharmacological properties is well established. However, similar concepts have not been applied to oligosaccharides. Here, we describe the design, synthesis, and characterization of the first stapled oligosaccharides. Automated assembly of β-(1,6)-glucans equipped with two alkenyl side chains was followed by on-resin Grubbs metathesis for efficient ring closure with a variety of cross-linkers of different sizes. O ...[more]

PMID: 36173281

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