Synthesis of LewisX-O-Core-1 threonine: A building block for O-linked LewisX glycopeptides. (27th November 2017)

• Record Type: Journal Article
• Authors: Sardar, Mohammed Y.R.; Krishnamurthy, Venkata R.; Park, Simon; Mandhapati, Appi Reddy; Wever, Walter J.; Park, Dayoung; Cummings, Richard D.; Chaikof, Elliot L.
• Is Part Of: Carbohydrate research. Volume 452(2017)
• Page Start: 47
• Page End: 53
• Publication Date: 2017-11-27
• Subjects: Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2017.10.002
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: Lewis X (Le X ) is a branched trisaccharide Galβ1→4(Fucα1→3)GlcNAc that is expressed on many cell surface glycoproteins and plays critical roles in innate and adaptive immune responses. However, efficient synthesis of glycopeptides bearing Le X remains a major limitation for structure-function studies of the Le X determinant. Here we report a total synthesis of a Le X pentasaccharide1 using a regioselective 1-benzenesulfinyl piperidine/triflic anhydride promoted [3 + 2] glycosylation. The presence of an Fmoc-threonine amino acid facilitates incorporation of the pentasaccharide in solid phase peptide synthesis, providing a route to diverse O -linked Le X glycopeptides. The described approach is broadly applicable to the synthesis of a variety of complex glycopeptides containing O -linked Le X or sialyl Lewis X (sLe X ). Graphical abstract: Highlights: Synthesis of Lewis X thioglycoside by iterative glycosylation. Regio- and stereoselective [3 + 2] glycosylation of the Le X donor to the Core 1 diol acceptor. Synthesis of Lewis X - O -Core-1 threonine pentasaccharide to access a wide array of Le X based glycopeptide analogues.