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Synthesis of LacNAcLe x ‐ and DimLe x ‐BSA Conjugates and Binding to Anti‐Polymeric Le x mAbs
Author(s) -
Nejatie Ali,
Jegatheeswaran Sinthuja,
Auzanneau FranceIsabelle
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901142
Subject(s) - chemistry , glycoconjugate , stereochemistry , tetrasaccharide , linker , glycoside , monomer , residue (chemistry) , molecule , iodide , disaccharide , polysaccharide , biochemistry , polymer , organic chemistry , computer science , operating system
The chemical synthesis of tetra‐ and pentasaccharide fragments of the tumor‐associated carbohydrate antigen dimeric Lewis X (dimLe x ) lacking either both or only the non‐reducing end fucosyl residues is described following a 1 + 1 + 1 synthetic strategy. Use of a 6‐chlorohexyl aglycon gave access to hexyl glycoside soluble inhibitors as well as the 6‐aminohexyl glycoside pentasaccharide. The 6‐aminohexyl glycoside pentasaccharide and a dimLe x analogue were conjugated to BSA via a squarate linker and the glycoconjugates were shown by MALDI MS to both display an average of 16 oligosaccharides per BSA molecule. These glycoconjugates were used in the attempt to identify the smallest dimLe x fragment required to maintain binding to mAbs SH2 and IG5F6, which are known to bind polymeric Le x structures preferentially over the monomeric Le x antigen. Titration studies showed that the non‐reducing end fucosyl residue in dimLe x is involved in the recognition of the antigen by both mAbs SH2 and IG5F6.