TY - JOUR

T1 - Synthesis of Type 1 Lewis b hexasaccharide antigen structures featuring flexible incorporation of L-[U-13C6]-fucose for NMR binding studies

AU - Long, Mark

AU - Ni Cheallaigh, Aisling

AU - Reihill, Mark

AU - Oscarson, Stefan

AU - Lahmann, Martina

PY - 2020/6/21

Y1 - 2020/6/21

N2 - While 13C-labelled proteins are common tools in NMR studies, lack of access to 13C-labelled carbohydrate structures has restricted their use. L-fucose is involved in a wide range of physiological and pathophysiological processes in mammalian organisms. Here, L-[U-13C6]-Fuc labelled type I Lewis b (Leb) structures have been synthesised for use in NMR binding studies with the Blood-group Antigen Binding Adhesin (BabA), a membrane-bound protein from the bacterium Helicobacter pylori. As part of this work, an efficient synthesis of a benzylated L-[U-13C6]-Fuc thioglycoside donor from L-[U-13C6]-Gal has been developed. The design and synthesis of an orthogonally protected tetrasaccharide precursor enabled controlled introduction of one or two 13C-labelled or non-labelled fucosyl residues prior to global deprotection. NMR analysis showed that it is straightforward to assign the anomeric centres as well as the H-5 positions to the individual fucosyl residues which are relevant for NMR binding studies

AB - While 13C-labelled proteins are common tools in NMR studies, lack of access to 13C-labelled carbohydrate structures has restricted their use. L-fucose is involved in a wide range of physiological and pathophysiological processes in mammalian organisms. Here, L-[U-13C6]-Fuc labelled type I Lewis b (Leb) structures have been synthesised for use in NMR binding studies with the Blood-group Antigen Binding Adhesin (BabA), a membrane-bound protein from the bacterium Helicobacter pylori. As part of this work, an efficient synthesis of a benzylated L-[U-13C6]-Fuc thioglycoside donor from L-[U-13C6]-Gal has been developed. The design and synthesis of an orthogonally protected tetrasaccharide precursor enabled controlled introduction of one or two 13C-labelled or non-labelled fucosyl residues prior to global deprotection. NMR analysis showed that it is straightforward to assign the anomeric centres as well as the H-5 positions to the individual fucosyl residues which are relevant for NMR binding studies

U2 - 10.1039/D0OB00426J

DO - 10.1039/D0OB00426J

M3 - Article

VL - 18

SP - 4452

EP - 4458

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 23

ER -