Synthesis of LacNAcLex- and DimLex-BSA Conjugates and Binding to Anti-Polymeric Lex mAbs

被引：4

作者：

Nejatie, Ali ^{[1
,2
]}

Jegatheeswaran, Sinthuja ^{[1
]}

Auzanneau, France-Isabelle ^{[1
]}

机构：

[1] Univ Guelph, Dept Chem, 50 Stone Rd East, Guelph, ON N1G 2W1, Canada

[2] Simon Fraser Univ, Dept Chem, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2019年 / 2019卷 / 39期

基金：

加拿大自然科学与工程研究理事会;

关键词：

Antigens; Glycoconjugates; Glycosylation; Oligosaccharides; N-ACETYLGLUCOSAMINE; PENTASACCHARIDE FRAGMENTS; ANTIBODIES; OLIGOSACCHARIDE; GLYCOSYLATIONS; TRISACCHARIDE; LOCALIZATION; LEWIS;

D O I：

10.1002/ejoc.201901142

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：6631 / 6645

页数：15