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Oligosaccharide Mimics Containing Galactose and Fucose Specifically Label Tumour Cell Surfaces and Inhibit Cell Adhesion to Fibronectin
Author(s) -
Kim Evelyn Y.L.,
Gronewold Claas,
Chatterjee Amitava,
von der Lieth ClausWilhelm,
Kliem Christian,
Schmauser Birgit,
Wiessler Manfred,
Frei Eva
Publication year - 2005
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.200400092
Subject(s) - fucose , chemistry , cell adhesion , fibronectin , biochemistry , stereochemistry , adhesion , cell culture , galactose , cell , biology , organic chemistry , genetics
With the aim of establishing a versatile and easy synthesis of branched saccharides for biological applications, we used molecular‐dynamics simulations to model Lewis y to two classes of di‐ or triantennary saccharide mimetics. One set of mimetics was based on 1,3,5‐tris(hydroxymethyl)cyclohexane (TMC) as the core, the other on furan, and both were derivatised with galactose and/or fucose. The TMC‐based saccharides were biotinylated, while the furan disaccharides were treated with maleimide‐activated biotin in a Diels–Alder fashion to yield oxazatricyclodecanes (OTDs). These were then assayed as cell‐surface labels in human colon (SW480 and CaCo‐2), liver (PLC), Glia (U333 CG 343) and ovary (SKOV‐3) tumour cell lines. Discrete staining patterns were observed in all cells, usually at one or two poles of the cells, particularly with the asymmetric 3‐β‐ L ‐fucopyranosyloxymethyl‐4‐β‐ D ‐galactopyranosyloxymethyl‐OTD. Normal SV40‐transformed fibroblasts (SV80) showed no staining. Adhesion of the highly metastatic mouse melanoma line B16 F10 to fibronectin was inhibited by 80 % by the TMC‐digalactoside and by 30 % by 3,4‐bis‐(β‐ D ‐galactopyranosyloxymethyl)furan. None of the saccharide mimetics inhibited the adhesion of the less metastatic B16 F1 line. Migration of B16 F10 cells through Matrigel TM was greatly inhibited by the TMC‐digalactoside and weakly inhibited by the TMC‐trigalactoside. The saccharide mimetics that had shown the best structural agreements with the terminal saccharides of Lewis y in the molecular dynamics simulation were also the most biologically potent compounds; this underlines the predictive nature of molecular dynamics simulations. The use of the non‐saccharide cores enabled us to adapt spacer lengths and terminal saccharides to optimise the structures to bind more avidly to cell‐surface lectins.