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Synthesis of N ‐Acetyllactosamine Derivatives with Variation in the Aglycon Moiety for the Study of Inhibition of Sialyl Lewis x Expression
Author(s) -
Mong Tony K.K.,
Lee Lac V.,
Brown Jillian R.,
Esko Jeffrey D.,
Wong ChiHuey
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200300650
Subject(s) - chemistry , sialyl lewis x , moiety , stereochemistry , biphenyl , derivative (finance) , selectin , organic chemistry , financial economics , economics , adhesion
Herein we describe an inhibition study of the sialyl Lewis x (sLe x ) expression on a human monocytic cell line (U937), using a series of peracetylated N ‐Acetyllactosamine (LacNAc) analogues with variation at the aglycon moiety. It was found that the extent of inhibition was related to the hydrophobicity and structure of the aglycon. In general, peracetylated LacNAc analogues with a naphthyl or biphenyl aglycon ( 3, 4, 6 , and 7 ) were better in suppression of sLe x expression than a benzyl derivative ( 2 ). Steady‐state kinetic experiments with human α‐1,3‐fucosyltransferases IV and VI (FucT IV and VI, EC 2.4.1.65) revealed that the deacetylated LacNAc‐aglycons with naphthyl ( 18, 19 , and 20 ) or biphenyl ( 17 ) moieties exhibited higher affinity to the fucosyltransferases than aglycon moieties with smaller hydrophobic groups ( 14, 15 , and 16 ). These results are in agreement with the findings of the U937 cell‐based experiments, and suggest that the higher enzyme affinity LacNAc‐aglycons make better acceptor decoys and, hence, the observed differences in LacNAc‐aglycon inhihitory effects on sLe x expression.