Parallel solution synthesis of a "Carbohybrid" library designed to inhibit galactose-binding proteins

Parallel solution S-alkylations of a 1-thio-beta-D-galactopyranoside derivative with Michael acceptors and alpha-chloroketones, followed by ketone reductions, reductive aminations, and acylations were developed to yield a library of 1-thio-beta-D-galactopyranosides carrying small and diverse polar-n...

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Bibliographic Details
Published in:	Combinatorial chemistry & high throughput screening Vol. 2; no. 6; p. 335
Main Authors:	Nilsson, U J, Fournier, E J, Fryz, E J, Hindsgaul, O
Format:	Journal Article
Language:	English
Published:	United Arab Emirates 01-12-1999
Subjects:	Calcium-Binding Proteins Carbohydrates - chemistry Combinatorial Chemistry Techniques Drug Evaluation, Preclinical - methods Galactose - chemistry Hemagglutination Tests Ketones - chemistry Lectins - drug effects Lectins - metabolism Monosaccharide Transport Proteins - antagonists & inhibitors Periplasmic Binding Proteins Stereoisomerism
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Summary:	Parallel solution S-alkylations of a 1-thio-beta-D-galactopyranoside derivative with Michael acceptors and alpha-chloroketones, followed by ketone reductions, reductive aminations, and acylations were developed to yield a library of 1-thio-beta-D-galactopyranosides carrying small and diverse polar-neutral, hydrophobic, aromatic, cationic, or anionic non-carbohydrate aglycon structures. Screening of the library against a panel of galactose recognizing plant lectins revealed microM inhibitors of toxin A of A. precatorius superior to the reference ligands lactose and N-acetyl lactosamine. Such small, monosaccharide based inhibitors are attractive lead-molecules for therapeutic development, since they are low-molecular, hydrolytically stable and more hydrophobic than natural oligosaccharides.
ISSN:	1386-2073
DOI:	10.2174/1386207302666220206123051