Synthesis and Glycan–Protein Interaction Studies of Se-Sialosides by ⁷⁷Se NMR

Abstract

To expand the potential of Se-carbohydrates for multifunctional mimicry of sugars, herein we addressed the synthesis of the highly challenging and biologically significant Se-glycosides of sialic acid (Se-sialosides). An α-sialyl selenolate anion generated in situ smoothly reacted with electrophiles to give α-Se-sialosides as single stereoisomers. A Se-sialoside was sequentially incorporated with selenium, producing a triseleno-sialoside. This molecule was used as a 77Se NMR-active handle for studying glycan–protein interaction, revealing different binding profiles of sialic acid binding proteins.

Synthesis of Diverse Seleno‐Glycolipids via the Transacetalization of Selenoacetals

“…Alkyl bromides of single‐chain lipids ( 7 – 13 ) were treated with BOMSeTol ( 6 ) in the presence of methylhydrazine and DIEA in DMF or in a DMF/THF (3 : 1) solvent mixture to give selenoacetals 15 – 21 (Table 1). [5i,10,11] Similarly, the alkyl iodide of double‐chain lipid 14 , which was readily prepared from 2‐tetradecyl‐1‐hexadecanol, was reacted with 6 in a DMF/THF (1 : 1) solvent mixture to produce selenoacetal 22 in high yield.…”

Heavy Atom Detergent/Lipid Combined X-ray Crystallography for Elucidating the Structure-Function Relationships of Membrane Proteins

“…The MeSe substitution disclosed the essential hydroxy group for interaction with the lectin. Currently, the selenium atom can be incorporated into an oligosaccharide structure, which facilitates applications of seleno probes to elucidate oligosaccharide binding to proteins by not only crystallography but NMR because 77 Se (I = 1/2, 7.6% natural abundance) is an NMR active nucleus that gives rise to a sharp signal [50]. Scheme 2.…”

Investigation of the Molecular Details of the Interactions of Selenoglycosides and Human Galectin-3

“…TDG displayed a comparable activity to the natural ligands of h Gal-3 [ 17 ] and was used extensively as a starting scaffold for further derivatives [ 19 , 20 , 21 , 22 , 23 ]. Selenium has been incorporated into carbohydrates to assist in X-ray crystal structure determination using single/multiple wavelength anomalous diffraction techniques [ 24 , 25 , 26 ] and also in NMR studies [ 27 , 28 , 29 ]. In our previous work, we proposed replacement of sulphur by selenium in digalactosides as a further bioisosteric substitution [ 30 ].…”